86 separate references and commentary follow this brief discussion.
SDR is an acronym for “sensory disruption of reconsolidation” of conditioned responses, and is an extremely rapid extinction strategy, quickly eliminating maladaptive feelings, thoughts and behaviours, and equally quickly producing more adaptive, solution-oriented thinking and behaviour. SDR achieves these changes without the client having to deliberately change or practice thinking styles, and is an extremely precise and robust therapy strategy.
We have been exploring, researching, developing and refining SDR for some two decades.
SDR has a powerful but nevertheless limited utility. It does not replace exploration of client issues, education of the client, collaborative creation of new communication strategies (for example), support for the client, and nor does it in any way negate the crucial value of the therapeutic alliance. What it does is speed and smooth therapy so that deeper, more satisfying and transformative outcomes are achieved more readily.
For example many problematic feelings, thoughts and behaviours can be quite literally extinguished in just minutes, allowing your therapy program to focus more on supporting solution-oriented navigation through the client’s environment, rather than spending so much time and energy on trying to change the client’s thinking or attitude. SDR makes both CBT and mindfulness completely superfluous.
For example, a client may be struggling with anger/aggression toward his wife, and he may even have hit her or been on the brink of that. By quickly eliminating that rage reaction (which is most certainly conditioned), you can now focus on communication and other issues to actually repair and enrich the relationship, if that is what the parties desire.
Another example is the non-malignant chronic pain client. Instead of trying to help the client to “live with” or “manage” their pain, you can now actually switch off pain signalling in most cases of non-malignant chronic pain. This frees you up to focus on the other issues which almost invariably accompany the chronic pain experience (or which may be maintaining pain signalling), without having to work through the client’s physical distress.
Disruption Vs Inhibition as an Extinction Strategy
Inhibition as a flawed extinction strategy for humans
From Pavlov and Watson, through to Skinner, Fordyce and others, inhibition strategies have been almost a single-minded focus of therapy, and currently are the basis for CBT (cognitive behaviour therapy), mindfulness, desensitisation, and others. The theory is that by inhibiting a response, the response will eventually weaken and the learned feelings, thoughts and behaviours will be reduced.
Indeed, CBT is often cited as the “gold standard” in therapy for a very wide range of issues and disorders.
However wherever one looks in the literature, whether it is a single study one is examining, or whole collections of meta-analyses, we see that the effect size for CBT is without exception described as moderate, weak, or even non-existent compared to placebo. As you will see in the references and commentary below, we cannot justify CBT as a “gold standard”. It is literally no better than having the client go for a 15-minute walk each day.
Inhibition strategies may produce strong effects in simple animal experiments in a lab, and may temporarily appear to work in your office, but they are not very helpful when it comes to complex people traversing complex environments.
Disruption of Reconsolidation – a fast and reliable extinction strategy
This is an extinction strategy first observed by Pavlov over 100 years ago, but the significance of which was not realised. He actually caused a conditioned response to fail immediately and permanently, in just seconds, but wrote it up as a failure of the response instead of as an incredible breakthrough.
Flash forward to modern times and we find that scientists are studying the exact same mechanism and have named it “disruption of reconsolidation of conditioned responses”. When that disruption is done with precision, it is capable of immediately and permanently extinguishing any conditioned response.
In our own trials we’ve seen efficacy rates well over 80%, when “efficacy” was measured as a +50% improvement, with that improvement being a reduction in pain levels, a reduction in diagnosed depression, or an improvement in academic and behavioural scores using data provided by teachers.
References and Commentary
The references and commentary below frequently refer to chronic pain, but are readily applicable to any amygdala-based disorder or emotional issue. Overwhelmingly, they demonstrate that no current treatment (pharmacological, psychological, physical therapy) is effective in reducing non-malignant chronic pain. Neither is there any significant clinical effect for other disorders. There is tremendous potential for improvement of outcomes if we will only move away from inhibition strategies, and move to rapid extinction via disruption instead.
1– Our own research. Two very small chronic pain trials were run. “Efficacy” was rated at pain reduction of 50% or more, and the trials achieved efficacy rates of 85% and 100% respectively. All participants achieved at least some reduction of pain, and over 62.5% achieved complete elimination of pain. Only one paper was prepared, with the paper from the second trial of 100% efficacy abandoned.
Similar methodology was utilised in an earlier paper on clinical depression, which was peer-reviewed and published by US academic journal Frontier Perspectives.
2–Machado G, et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials. BMJ 2015: 350:h1225
This meta-analysis screened over 4,000 titles and abstracts and concluded that paracetamol was ineffective for neck and lower back pain.
3– Machado G, et al. Non-steroidal anti-inflammatory drugs for spinal pain: a systematic review and meta-analysis. Ann Rheum Dis. 2017 Jul: 76(7):1269-1278
Weirdly, this study concludes that NSAIDs are effective for spinal pain, but in the same breath state they are no better than placebo! The paper also states “At present, there are no simple analgesics that provide clinically important effects for spinal pain over placebo. “
4– Turk DC. Clinical effectiveness and cost-effectiveness of treatments for patients with chronic pain. Clin J Pain. 2002 Nov-Dec;18(6):355-65.This important meta-analysis looked at a very wide variety of pain treatments and programs including pharmacological, physical therapies, CBT, and mindfulness. It noted that none of the treatments or programs achieved any significant outcome for some 70% of sufferers.Since we know that placebo effect can be quite high (regression to the mean, self-delusion, and other factors) the fact that 70% of people did not get any outcome, and that therefore 30% of people got “some” outcome (statistically significant is not necessarily clinically significant) is not good news.
5– https://www.health.nsw.gov.au/pharmaceutical/doctors/Pages/chronic-pain-medical-practitioners.aspx.It is so widely recognised that chronic pain can often not be eliminated that physicians are guided to help the patient achieve management of the pain, rather than elimination of the pain.
6– Machado, L, et al. Analgesic effects of treatments for non-specific low back pain: a meta-analysis of placebo-controlled randomized trials. Rheumatology (Oxford). 2009 May;48(5):520–7.This meta-analysis examined a very wide range of current treatments for back pain, carefully selecting quality studies which were well designed, and which were utilising placebo interventions which avoided skewing results. They concluded that no treatments achieved results any better than placebo.
7– Blyth, F, Huckel Schneider, C. Global burden of pain and global pain policy—creating a purposeful body of evidence PAIN: September 2018 – Volume 159 – Issue – p S43–S48.
Although the figure of 1.5 billion chronic pain sufferers is not explicitly stated, it can be extrapolated in terms of percentage of population. So far as I’m aware this is an estimate which is not disputed.
8– Nilay, S, Ali Yavuz, K, İlknur, A, Turk, J. Effectiveness of physical therapy and exercise on pain and functional status in patients with chronic low back pain: a randomized-controlled trial.
Phys Med Rehab 2018;64(1):52-58I included this paper because it is up to date and representative of papers purporting to demonstrate benefit of physical therapy for chronic pain. In fact if you delve into the data you will see that there was an average <25% reduction in reported pain, ie the average VAS went from 6.1 to 4.7, whereas the control group went from 5.2 to 5.0. No-one has demonstrated that physical therapy programs for chronic pain are in any way superior to merely increasing socialisation and activity levels.
There are a number of papers being disseminated throughout the physiotherapy space right now, asserting that various physiotherapeutic protocols are effective for chronic pain. I note that so far not a single one compares a therapeutic protocol with merely remaining active with the support of an empathetic professional. But that hasn’t stopped the commercialisation of unnecessary protocols.
9– Smit, T, Harrison, R. Hydrotherapy and Chronic Lower Back Pain: A Pilot Study. Australian Physiotherapy 37(4), 229-234. (1991).
Lower back pain is the most prevalent of chronic pain presentations and by now there are a considerable number of studies which show benefit while the patient is actually in a hydrotherapy program. However any reduction in pain appears to disappear within 90 days of completion.
10– Brinjikji, et al. Systematic Literature Review of Imaging Features of Spinal Degeneration in Asymptomatic Populations. AKMR Am J Neuroradiolv 2015; 1-6.
This review examined 33 articles looking at MRI results for over 3000 people who were not experiencing any pain. It found disc degeneration, disc bulge, disc protrusion, and annular fissure in as many as 96%.
11– Ingraham, P. MRI and X-Ray Often Worse than Useless for Back Pain. Pain Science, April 14, 2018.
This article includes further excellent references relating to physician guidelines and studies which demonstrate no link between imaging and chronic pain presentation.
12– Rajeswaran, G, Turner, M, Gissane, C, Healy, J. MRI findings in the lumbar spines of asymptomatic elite junior tennis players. Skeletal Radiol. 2014 Jul;43(7):925-32.
There have been other studies like this one, so this is representative. Only 4% of these elite performers were without abnormality. Over 62% had disc degeneration, and over 30% had disc herniation. Other “problems” identified were facet joint arthropathy, synovial cysts, and nerve root compression. We now know that there is not much difference in the health of spines of top performing athletes who do not have pain, and people who are suffering from chronic pain. This should tell us that this type of chronic pain is not usually about pathology (which doesn’t mean that it can’t be, just that it usually is not). My great fear around this is happening right now, with doctors refusing to believe that their patient has pain, and in turn refusing to provide pain relief. In extreme cases (mainly in the USA) we’re seeing pain relief refused even after major surgery, and people on their death bed dying in agony because they’re refused pain relief even then.
13– Moseley, G, Vlaeyen, J. Beyond nociception: the imprecision hypothesis of chronic pain. Pain. 2015, vol 156, no 1.
Moseley and Vlaeyen, widely respected in the chronic pain arena, make their case for an understanding of chronic pain that is not linked to pathology (ie; the pain is non-nociceptive) and provide an extensive array of citations to support their hypothesis. Interestingly, their studies which attempted to demonstrate that pain education was in itself sufficient to reduce pain perception, failed. Inhibiting pain behaviour does not inhibit pain perception.
14– Wolf, B, Buckwalter, J. Randomized Surgical Trials and “Sham” Surgery: Relevance to Modern Orthopaedics and Minimally Invasive Surgery. Iowa Orthop J. 2006; 26: 107–111.
This interesting systematic review explores ethical issues of sham surgery and also reports results of several trials (there are not many) involving sham surgery which demonstrate undifferentiated outcomes. I have not been able to find any meta-analysis showing surgery as superior to sham surgery for chronic pain. By now this absence of outcomes from surgery is well accepted and routine surgery for chronic pain is no longer recommended.
15– https://www.health.harvard.edu/pain/babying-your-back-may-delay-healing Interesting points about back pain:
Back pain is weird – it tends to go away even when damage remains (much like you can’t detect the perfume you put on only 10 minutes ago)
Disc problems increase with age, and more pain due to disc problems (eg bulging) are reported in 40 and 50-year-olds. However after that, despite increasing rates of spinal problems, there is less pain reported.
Back pain is recognised as being neurological, rather than being related to actual damage.
16– López-de-Uralde-Villanueva, I, Muñoz-García, D, Gil-Martínez, A, Pardo-Montero, J, Muñoz-Plata, R, Angulo-Díaz-Parreño, S, Gómez-Martínez, M, La Touche, R. A Systematic Review and Meta-Analysis on the Effectiveness of Graded Activity and Graded Exposure for Chronic Nonspecific Low Back Pain.Pain Med. 2016 Jan;17(1):172–88.
See comment below for (17).
17– Frost, H, Lamb, S, Doll, H, Taffe Carver, P, Stewart-Brown, S. Randomised controlled trial of physiotherapy compared with advice for low back pain. BMJ 23 Sept 2004.
16 and 17 demonstrated that when it comes to chronic pain, physiotherapy has no clinical benefit beyond any other increase in activity levels. Literally any kind of exercise is helpful to low back pain patients, and people who take up an active hobby do even better than people who simply enter a physiotherapy program.
18– Lasselin, J, et al. Low-grade inflammation may moderate the effect of behavioral treatment for chronic pain in adults. J Behav Med, 2016.39:916-24.
The purpose of this study was actually to explore a link between higher inflammation levels and poorer outcomes for chronic pain patients enrolled in CBT programs. Similar to other studies, the data revealed that concentrations of inflammatory factors in chronic pain conditions are overall insignificantly higher than in healthy populations, and remain in the healthy ranges.
There is not yet a definitive link between inflammation and chronic pain except in levels of inflammation above normal ranges, and even then it is thought possible that sensitisation may create inflammation, just as it is possible that inflammation may lead to sensitisation. In other words, inflammation as a cause of chronic pain remains unproven, and it could be that the same process that creates the pain, creates the inflammation.
Nevertheless, where pathology has been ruled out, and where chronic pain persists despite treatment with the SDR program, it would seem wise to check whether inflammation levels are higher than normal range, in case that rare probability is a factor.
19– Achterberg, W, et al. Pain management in patients with dementia. Clin Interv Aging. 2013; 8: 1471–1482.
This study looked at reasons for increasing rates of dementia, and included data around increased risk of chronic pain amongst this group due to increased falls, accidents etc and puts the prevalence of chronic pain at a massive 50%. Commentary was made around the difficulty of adequately treating this group due to communication challenges, and also due to the older generation often being unwilling to complain, or being stoic. I personally have worked with only one chronic pain client with dementia, and failed miserably to get any improvement. This was complicated by the fact that the client, although verbal, was unable to say whether or not she had pain at any time.
20– Soeter, M, Kindt, M. Disrupting reconsolidation: Pharmacological and behavioural manipulations. Learn. Mem. 2011. 18: 357-366
This clinical trial demonstrated that it was possible to implement an extinction procedure within the window of reconsolidation in order to successfully eliminate a conditioned response.This is a very exciting advance in current knowledge about extinction and provides a solution which is more practicable and also much faster and more gentle than other methods (inhibition, flooding) used to date. We had been working on this method of extinction since 1992, so to see researchers delving deep into the neuroscience behind our theory was beyond exciting to us.
21– Cathy O’Leary (Medical Editor). Warning as health insurance costs bite. The West Australian, 20 June 2018.
This article detailed statistics relating to unsustainable costs of providing medical treatment. We cannot afford to keep using inefficient treatment methods for chronic pain, or for issues such as overweight/obesity, depression, anxiety, addiction, etc.
22– Enke, O, et al. Anticonvulsants in the treatment of low back pain and lumbar radicular pain: a systematic review and meta-analysis. CMAJ July 03, 2018 190 (26) E786-E793.
There is moderate- to high-quality evidence that anticonvulsants are ineffective for treatment of low back pain or lumbar radicular pain. There is high-quality evidence that gabapentinoids (Lyrica is one you may commonly see prescribed) have a higher risk for adverse events.
23– Krebs, E. Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) Trial. Minneapolis VA Health Care System, Minneapolis, MN. May 2017
This study followed 240 patients over a 12-month period and found that opioids were no better than non-opioid medication for chronic back pain or hip or knee osteoarthritis, following 240 patients over a 12-month period. With other studies showing that non-opioid medication is similarly ineffective, this does not bode well for the state of medication for chronic pain.
However, this does not mean that we should disbelieve pain patients who are stable, safe and functioning on opioids because the opioids are effective for them as individuals. It’s been deeply disturbing to read the anti-opioid zealotry which has taken hold in pain treatment and to witness the gross harm being done when pain relief is refused.
24– De Vita, M, et al. Association of Cannabinoid Administration with Experimental Pain in Healthy Adults, A Systematic Review and Meta-analysis. JAMA Psychiatry, September 19, 2018.
This systematic review and meta-analysis of 18 separate studies showed that while cannabis could raise the pain threshold minimally prior to being given a painful stimulus, it had no effect at all on the intensity of pain, reduced perceived unpleasantness of pain, and no reduction of mechanical hyperalgesia.
25– Mammen, G, et al. Association of Cannabis With Long-Term Clinical Symptoms in Anxiety and Mood Disorders: A Systematic Review of Prospective Studies. J Clin Psychiatry.2018 Jun 5;79(4). pii: 17r11839.
Over 10,000 citations screened, 12 studies accepted (with a total of 11,959 individuals) met inclusion criteria related to posttraumatic stress disorder (n = 4), panic disorder (n = 1), bipolar disorder (n = 5), and depressive disorder (n = 2).
Across 11 studies, “recent” cannabis use (ie, any/greater frequency of use during the last 6 months) was associated with higher symptomatic levels over time relative to comparison groups (ie, no/lesser frequency of use). Ten of these studies further suggested that cannabis use was associated with less symptomatic improvement from treatment (eg, medication, psychotherapy for AMD).
This study concluded: “Recent cannabis use was associated with negative long-term symptomatic and treatment outcomes across AMD. The findings should be interpreted with caution, considering the observational designs across studies and the biases associated with the samples (eg, inpatients) and sources of cannabis consumed (ie, unregulated sources). Nonetheless, clinicians can use the insight gained to inform their own and their patients’ knowledge concerning potential risks of cannabis with regard to symptoms of AMD.”
26– Hill, P, Palastro, B, Ditre, J. Cannabis and Pain: A Clinical Review. Cannabis Cannabinoid Res. 2017; 2(1): 96–104.
This meta-analysis, while referring to reduced opioid use and other benefits when cannabinoids were used as an opioid alternative, also refers to increased pain levels for some users.
27– Campbell, G, et al. Effect of cannabis use in people with chronic non-cancer pain prescribed opioids: findings from a 4-year prospective cohort study.
The Lancet Public Health, July 1, 2018, Vol 3, Issue 7. This Australian study is one of the largest and longest to date. Researchers at the UNSW Sydney examined the effect of cannabis on 1500 Australians who were already part of research on treating pain through prescription opioids. This study found that non-cancer pain sufferers who used available street-market cannabis had higher pain levels than those who did not use cannabis. It also found no evidence of reduction of opioid use.
28– Wallace, M, et al. Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers. Anesthesiology.2007 Nov;107(5):785-96.
This study, although on healthy volunteers, demonstrated a mechanism whereby cannabis could both increase or decrease pain.
Although many people report lowered pain levels in the use of cannabinoids, it is quite clear that cannabinoids can also make pain worse, and that the dosage patterns are not linear – it’s not simply a matter of more is better, and it’s not even that researchers have been able to identify a “sweet spot”. The outcomes of this trial look more like random “results” which is exactly what we’d expect if there was no real effect and people were simply experiencing the normal ebb and flow of pain. This is why so many medical practitioners are still loathe to prescribe it. We simply do not have enough understanding of the mechanisms around cannabis, cannabinoid receptors, and chronic pain, and most doctors will not prescribe something that has no robust evidence, and yet has potential to leave their patient in even worse agony.
29– Grace, P, et al. Repeated Morphine Prolongs Postoperative Pain in Male Rats. Anesthesia & Analgesia: March 27, 2018 – Volume Publish Ahead of Print.Link: https://journals.lww.com/anesthesia-analgesia/Abstract/publishahead/Repeated_Morphine_Prolongs_Postoperative_Pain_in.96846.aspx
This study found that use of morphine could extend suffering from pain after surgery, and may make pain worse. It is thought that opioids increase the inflammation response, so that pain signalling actually increases. This may explain why some people coming off opioids report reduced pain levels.
Unfortunately, digested undiscerningly, this study has led to a belief that “morphine makes pain worse”.
30– Grace, P, et al. Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation. Proc Natl Acad Sci U S A.2016 Jun 14;113(24):E3441-50.
This study found that use of morphine could extend suffering from pain after injury. “Could”. A single study, once again from an anti-opioid bias, and in rats, not people. It may be that for some people opioids can make pain worse but it would be a grave error to jump to a conclusion that this is true for all patients on opioids.
31– Williams, C, Maher, C, Hancock, M, et al. Low back pain and best practice care: A survey of general practice physicians. Arch Intern Med 2010;170(3):271–77.
This study showed that opioids are no better than simple analgesics and lead to worse pain.
32– Maher, C. Williams, C, Lin, C, Latimer, J. Managing low back pain in primary care, Aust Prescr 2011;34:128-321 Oct 2011
This study surveyed doctors involved in primary care of low back pain in Australia.
Low back pain is the second most common reason to visit the doctor (with the common cold being the primary reason). Only about 50% of people who experience low back pain go to see their doctor for this issue. Of those, 94% of LBP patients are diagnosed as non-specific, meaning that no pathology has been identified which can sufficiently account for the pain. Of those people, only 18% are given advice about the importance of remaining active. The majority are prescribed NSAIDs or opioids (57%) and 20% are prescribed simple analgesics such as paracetamol. Some 20% of LBP patients go on to develop chronic pain.
This study re-affirms the well-accepted fact that most people with low back pain experience spontaneous resolution of their pain within 1 or 2 weeks, provided they remain active and use appropriate doses of simple analgesics, and that physical therapy (physiotherapeutic intervention) is not generally of benefit. It also repeats the well-accepted fact that some 20% of people will not respond to any treatment and their pain becomes chronic in nature. These are the people who can benefit, usually quite rapidly, from SDR Therapy.
33– I have made the statement that most pain clinics do not purport to reduce pain levels, and instead say that their focus is on helping clients to manage their pain, so that they optimise their quality of life despite the pain. Here are some actual quotes from clinic web sites which demonstrate this rather awful state of affairs.
“We work closely with you and a multidisciplinary team to ensure your pain is identified and managed appropriately.”
“Delivering a complete recovery program for people with chronic pain without using opioids and based on the latest scientific evidence.”
“We are honest and Genuinely CARE about you and your problem.”
“The aim is not to live pain free, but to live fully by managing the pain.”
No-one is talking about switching off pain signalling in cases of chronic pain, or even about reducing pain. Because they can’t.
34– Goyal, M, et al. Meditation Programs for Psychological Stress and Well-being, A Systematic Review and Meta-analysis. JAMA Intern Med. 2014;174(3):357-368.
This major meta-analysis actually screened over 19,000 citations and could find only 47 that were of sufficient quality to analyse. Despite stating that mindfulness could achieve “small-to-moderate” benefit, this was not supported by the data, and the authors themselves noted “In our comparative effectiveness analyses, we found low evidence of no effect or insufficient evidence that any of the meditation programs were more effective than exercise, progressive muscle relaxation, cognitive-behavioral group therapy, or other specific comparators in changing any outcomes of interest.”
Allan Goroll, a doctor at Harvard University said: “Contrary to popular belief, the studies overall failed to show much benefit from meditation with regard to relief of suffering or improvement in overall health.”
35– Linton, S, Shaw, W. Impact of Psychological Factors in the Experience of Pain. Physical Therapy, Volume 91, Issue 5, 1 May 2011, Pages 700–711.
There is no doubt that many people believe a positive attitude is beneficial to health in general, and beneficial in terms of therapy outcomes. In fact most studies purport to show that this belief has a scientific basis. However this paper pinpoints the major problem with research around positive/negative affect and chronic pain. Most studies are done with a clear intention of proving the benefit of positive affect, but none are talking about actual reduction of pain. All are talking about pain resilience.
Placebo effect does not translate to biological change. And manipulating patients into shutting up about their suffering is not therapy.
36– Morley, S, Williams, A, Eccleston, C. Examining the evidence about psychological treatments for chronic pain: Time for a paradigm shift? Pain, 2013, Vol. 154, No. 10, pp. 1929-1931.
Just like many studies of CBT, this study purported to show the effectiveness of CBT in enhancing positive affect and thereby achieving higher pain resilience. In marked contrast to that claim, it actually includes the statement “Half of the comparisons showed no effect of CBT and half showed weak effect sizes of unknown clinical significance on pain, mood, disability and catastrophic thinking outcomes.” To put this in plain language: half of the participants had improvement so small it couldn’t even be measured, and half definitely got zilch. In other words, the result was a big, fat nothing.
I honestly don’t know how this bunk gets published.
37– Average salary of a psychologist in Australia is around $75,000 per annum.https://www.payscale.com/research/AU/Job=Clinical_Psychologist/Salary
While it’s not uncommon for psychologists to earn in excess of $150,000 per annum, there are also many who a lot less than the average of $75,000. The primary reason for this is that practices are subsidising client care by undercharging. I’ve added this as part of an argument that therapists should be placing clients in longer and more transformative programs, rather than engaging on a session-by-session basis, and that practice development deserves wider support. This is not about milking the client, but about achieving the outcomes the client wants and has a human right to enjoy.
38– Interview with Alf L Nachemson, conducted by Mark L Schoene in Washing DC on April 1, 2006 and revised December 6, 2006. Chronic pain not explained or fully explained by pathology.Read online at http://links.lww.com/BRS/A300.
Professor Nachemson is widely respected as a pioneer in the area of back pain and his hundreds of research papers have been cited by other researchers worldwide. He was one of the first researchers to recognise that pain was not always linked to pathology, that other factors, such as biosocial factors, played a significant role, and that the brain was intimately involved in pain perception.
This wide-ranging interview toward the end of his life speaks to many of the principles I discuss in the main text for our training program and is an excellent defense of the concept of non-nociceptive pain.
39– Fleming, K, Volcheck, M. Central Sensitization Syndrome and the Initial Evaluation of a Patient with Fibromyalgia: A Review. Rambam Maimonides Med J. 2015 Apr; 6(2): e0020.
This study notes that central sensitisation can give rise to a very wide variety of symptoms quite apart from chronic pain, hyperalgesia, allodynia and generalisation, and can impact on virtually any function of the body, including inflammation, hormone production, and others. In fact it lists 64 different medical and/or psychological disorders that may result from central sensitisation.
40– Is Fibromyalgia an immune disorder? https://www.healthline.com/health/is-fibromyalgia-an-autoimmune-disease
It used to be thought that fibromyalgia was an immune disorder, but this is no longer the case. Sometimes an immune disorder may also be present, but this is more likely an effect of central sensitisation rather than an immune disorder per se. This is why it may no longer be appropriate to be managed by a rheumatologist. In fact Canada has proscriptions in place against rheumatologists being involved in treating fibromyalgia. They are told quite clearly that it is outside their scope of practice. (See 41 below.)
41– Ingraham, P. A Rational Guide to Fibromyalgia: The science of the mysterious disease of pain, exhaustion, and mental fog. https://www.painscience.com/articles/fibromyalgia.php.
This comprehensive article explains the weirdness of fibromyalgia. The 71 citations and end-notes lead to excellent further reading.
42– Wahezi, S, Algra J. Epigenetic Pain Regulation. J Clin Epigenet. (2017) Vol. 3 No. 4:37
This paper describes mechanisms whereby in response to pain, DNA can direct production of more sensors, which are in turn more sensitive to pain. This is possible support for the aphorism “pain leads to more pain”.
43– Ladron de Guevara, C, Fernandez-Serrano, M, Reyes del Paso, G, Duschek, S. Executive function impairments in fibromyalgia syndrome: Relevance of clinical variables and body mass index. PLOS ONE, April 25, 2018.
This study confirms the existence of mental impairment known as “fibro fog” that is common in fibromyalgia, arthritis, and other disorders which are sensorially overwhelming.
44– Arnsten, A. Stress signalling pathways that impair prefrontal cortex structure and function. Nat Rev Neurosci. 2009 Jun; 10(6): 410–422.
A scholarly article which explains how the brain reacts to stress by reducing activity in the prefrontal cortex and increasing activity in the “reptilian” brain as part of the fight/flight/freeze reflex, and simultaneously reducing cognitive ability.
45– Durmer, J, Dinges, D. Neurocognitive consequences of sleep deprivation. Semin Neurol.2005 Mar;25(1):117-29.
While it certainly seems logical that sleep deficiencies lead to impaired mental and physical capacity, and many of us have experienced exactly that, as you’ll see in the above paper, the scientific evidence is also sound.
I chose this paper from amongst others because so many involve extremely short-term sleep deprivation amongst students (a very easy-to-access study population) and these find slowing of mental processes, but no reduction in cognitive ability, meaning that although the person took longer to do a test, test performance remained just as accurate as prior to sleep deprivation. Those very short-term studies of young and healthy people may not be relevant to those suffering ongoing sleep dysfunction, especially if their health is already compromised.
46– Khadilkar, A, Odebiyi, D, Brosseau, L, Wells, G. Transcutaneous electrical nerve stimulation (TENS) versus placebo for chronic low-back pain. Cochrane, October 2008.
Cochrane Reviews are systematic reviews of primary research in human health care and health policy, and are internationally recognised as the highest standard in evidence-based health care. They investigate the effects of interventions for prevention, treatment and rehabilitation.
This particular review stated “Low-back pain (LBP) represents a leading cause for work absenteeism and visits to health care professionals. Sixty to 90% of the adult population is at risk of developing LBP. While the majority of episodes appear to resolve within six weeks, recurrences are common. In addition, it is estimated that 10% to 20% of affected adults develop symptoms of chronic LBP (persistent pain lasting longer than three months). Chronic LBP has a significant impact on everyday life. Transcutaneous electrical nerve stimulation (TENS) is widely used as a supplemental therapy in the management of LBP. It is a relatively safe, non-invasive and easy to use treatment option. TENS units deliver electrical stimulation to the underlying nerves via electrodes placed over the intact skin surface near the source of maximal pain.
Four high-quality randomized controlled trials (RCTs; 585 patients) comparing TENS with placebo for chronic low-back pain were included in this study. Due to conflicting evidence, it is unclear if TENS is beneficial in reducing back pain intensity. However, there was consistent evidence in two trials (410 patients) that TENS did not improve the level of disability due to back pain. There was moderate evidence that use of medical services and work status (e.g. loss of work, sick days) did not change during treatment. Finally, there did not seem to be a difference between conventional and acupuncture-like TENS. Some adverse effects were reported, typically minor skin irritations observed equally in the treatment and placebo groups. However, there was one participant who developed a severe rash four days after the start of treatment.
In summary, the review authors found conflicting evidence regarding the benefits of TENS for chronic LBP, which does not support the use of TENS in the routine management of chronic LBP.”
47– Rajan Samuel, S, Arun Maiya, G. Application of Low Frequency and Medium Frequency Currents in the Management of Acute and Chronic Pain-A Narrative Review. Indian J Palliat Care. 2015 Jan-Apr; 21(1): 116–120.
This meta-analysis actually attempts to make a case in favour of TENS, even though it also states that research methodology is particularly flawed. 15 out of 17 randomised controlled trials showed that TENS was no better than placebo.
48– Author names withheld to avoid embarrassing them. Treating Chronic Pain Using the (Brand name for PEMF device withheld so I don’t get sued): A double-blind clinical trial with placebo.
I cannot find any evidence of peer-review for this single trial, which the company claims is evidence that the device reduces pain. There were only 39 participants, with 9 (23%) withdrawing prior to the trial end because they felt they got no result at all.
By avoiding giving actual pain scores (the usual VAS method which you’ll be so familiar with) and using an exaggerated chart to make completely insignificant results look large, they claim that the treatment group had significantly less pain.
However they also state “Group differences (between placebo and treatment groups) were nonsignificant”. Indeed they were nonsignificant, as pain levels in the placebo group dropped by 0.1 and pain levels in the treatment group dropped 0.9. This is not even a difference of a single point and could be easily explained by random/flawed subjective assessment, or more likely, the normal ebb and flow of the pain experience.
They cheekily omitted the 9 complete failures from these results, in order to get even a measly <0.8 points of difference in scoring! It’s highly likely that 100% of the group experienced less than even 10% pain reduction.
Add to this the fact that over a 2-week period these types of chronic pain will fluctuate in any case, and the fact that regression to the mean must be taken into account, this makes a mockery of the whole “trial”.
In another “trial” in Perth, independent from company influence, 6 individuals with chronic pain were given devices to test. All 6 returned the device saying that it did nothing and was basically “placebo bullshit”.
Nevertheless, glowing testimonials from deluded customers assist to keep selling it. In another “study” which I dug out on this device (apparently so bad that the company don’t even now mention that one, if they ever did), 10 people were included in the group. 5 of them got no reduction in their pain whatsoever. The remaining 5 apparently got somewhere between 0 and 94% improvement. No details are given, and it’s highly possible that of the 5 who are claimed to have got a result, 1 person got 94% (because of regression to the mean) and the rest got less than 1%. We don’t know because they’re not telling.
If trials get actual results, researchers don’t hide the data, they crow about it.
This article examines the wild claims made by sellers of PEMF devices and shows why they are complete and utter snake oil.
50– Hong-fei, S, et al Early application of pulsed electromagnetic field in the treatment of postoperative delayed union of long-bone fractures: a prospective randomized controlled study.. BMC Musculoskelet Disord. 2013; 14: 35.
On the face of it, it appears that PEMF may be useful in just one very limited way, and that is the healing rate of one specific type of bone fracture. (Ie, not for any other type of tissue healing whatsoever.)
If you actually read this particular study, you’ll see that it’s not that remarkable anyway, with a failure rate of over 30%, and only slightly faster healing than a sham treatment group, taking months in any case. Keep in mind that when researchers use the word “significant” they are talking about statistical significance. A significant difference in numbers does not necessarily mean a significant difference in actual outcome. Statistical significance does not necessarily mean clinical significance.
There may one day be a way to significantly speed healing rates of bone and tissue, but we don’t have it yet.
51– Dunsmoor, J, et al. Rethinking extinction. Neuron. 2015 October 7: 88(1): 47-63
Please do read this one – made my heart sing. It’s a beautiful summary of classical conditioning to date, together with an updated understanding.
According to the World Health Organisation, “physical inactivity (lack of physical activity) has been identified as the fourth leading risk factor for global mortality (6% of deaths globally). Moreover, physical inactivity is estimated to be the main cause for approximately 21–25% of breast and colon cancers, 27% of diabetes and approximately 30% of ischaemic heart disease burden.”
53– Jonas, W, et al. Are Invasive Procedures Effective for Chronic Pain? A Systematic Review.Pain Med.2018 Sep 10.
This paper concluded: “There is little evidence for the specific efficacy beyond sham for invasive procedures in chronic pain. A moderate amount of evidence does not support the use of invasive procedures as compared with sham procedures for patients with chronic back or knee pain. Given their high cost and safety concerns, more rigorous studies are required before invasive procedures are routinely used for patients with chronic pain.”
54– Borsook, D, et al. Surgically-Induced Neuropathic Pain (SNPP): Understanding the Perioperative Process. Ann Surg. 2013 Mar; 257(3): 403–412.
While a nerve branch may be cut as a last resort, and may give initial relief, it can also immediately or shortly make the pain worse, for the simple fact that cutting a nerve equals damaging a nerve, and inflammation and other factors, together with undifferentiated regrowth, can be devastating. It really is a last resort, may not work, can make the pain worse, and can substantially affect mobility.
55– Lim, J, et al. CBT for chronic pain. Medicine (Baltimore). 2018 Jun; 97(23): e10867.
Like most studies investigating CBT for chronic pain, this one is flawed by not having an appropriate control group such that outcomes could be compared with a group utilising some other treatment (eg physical therapy). Nevertheless the results were completely unimpressive.
56– Holahan, c, et al. Stress Generation, Avoidance Coping, and Depressive Symptoms: A 10-Year Model. J Consult Clin Psychol. 2005 Aug; 73(4): 658–666.
This study demonstrated that avoidant coping tending to be associated with higher levels of distress, which endured over a longer period. It made no mention of the fact that people experiencing very high pain are likely to be less active than people with lower levels of pain.
57– Hofmann, S, et al. The Efficacy of Cognitive Behavioral Therapy: A Review of Meta-analyses. Cognit Ther Res. 2012 Oct 1; 36(5): 427–440.
This large review of meta-analyses is typical unfortunately. It first makes a claim that CBT has strong evidence, but then provides data and conclusions which demonstrate that CBT has a weak effect compared with waiting list or no treatment, and is not at all effective in many cases.
This is actually especially damning because we know that pretty much anything usually performs better than a waiting list, for several reasons. So in this case, to have such a weak effect is even less than what we would have expected from literally any other intervention.
58– Faucett, K, et al. A Systematic Review of Comparative Efficacy of Treatments and Controls for Depression. PLoS ONE 7(7): e41778.
This major meta-analysis reviews several different types of treatment and reports that in blind studies all interventions, including CBT, are better than doing nothing but none are more effective than placebo.
59– Krupnick, J, et al. The role of the therapeutic alliance in psychotherapy and pharmacotherapy outcome: findings in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. Journal of Consulting Clinical Psychology, 1996, 64(3): 532-9 (June).
Trends in psychotherapy research suggest that rather than there being a standardised psychotherapeutic or pharmacological ‘magic bullet’ intervention, it is the quality of the therapeutic alliance as assessed subjectively by the client, that is the most significant variable in the determination of treatment outcome.
60– Semple, R, Droutma, V, Reid, B. Mindfulness goes to school: things learned (so far) from research and real-world experiences. Psychol Sch. 2017 Jan; 54(1): 29–52.
See comments under 61, below.
61– Farias, M, Wikholm, C. Has the science of mindfulness lost its mind? BJPsych Bull. 2016 Dec; 40(6): 329–332.For 60 and 61.
These 2 meta reviews first purport that mindfulness is beneficial, but then admit that research has been problematic, and that results are insufficient, or may even demonstrate harm.
62– Van Dam, N, van Vugt, M, Vago, D. Mind the Hype: A Critical Evaluation and Prescriptive Agenda for Research on Mindfulness and Meditation. Perspect Psychol Sci.2018 Jan;13(1):36-61
Fifteen prominent psychologists and cognitive scientists caution that despite the hype and popularity, actual scientific data on mindfulness is lacking. The authors claim that studies are poorly designed and compromised by inconsistent definitions, and fail to include an appropriate control group to rule out placebo effect. Mindfulness has not been shown to be any better than a brief nap.
63– Sharf, R. Is mindfulness Buddhist? (and why it matters). Transcult Psychiatry.2015 Aug;52(4):470-84.
Buddhists disagree with claims of benefit from mindfulness. Robert Sharf is a Distinguished Professor of Buddhist Studies in the Department of East Asian Languages and Cultures at the University of California. In this paper he critiques claims of benefit.
64– Lindahl, J, et al. The varieties of contemplative experience: A mixed-methods study of meditation-related challenges in Western Buddhists. Plos One, May 24, 2017.
Mindfulness can lead to panic attacks, anxiety and depression. This study, like most studies around mindfulness, had its flaws. However despite the lead researcher being a believer in positive outcomes from mindfulness, in this paper he describes some very negative outcomes. If you place this in the context of endnote 63 above, you will see that distress following meditation has been well-known amongst practising Buddhists, and is even regarded by some as part of the journey toward enlightenment.
65– Gunnar, M. Perspectives on Psychological Science: Right Way/Wrong Way Symposium. July 20, 2017, Association for Psychological Science.
There is a view that misinformation and propaganda around mindfulness are not only misleading people, but also holding back the field of psychology.
66– Moffet, H. Sham acupuncture may be as efficacious as true acupuncture: a systematic review of clinical trials. J Altern Complement Med. 2009 Mar;15(3):213-6.
Acupuncture – put the damn needles anywhere. In trial after trial we see that it doesn’t matter where the needles are placed, or even whether needles are used. All that happens, if anything, is an expected placebo response, but no physiological change. In other words, some people temporarily fool themselves that they feel better, but not because of the acupuncture. No actual benefit is achieved.
In any other field the results experienced in this trial would have been interpreted as a failure. However, in deep misunderstanding about what placebo actually is, instead the researchers concluded that since sham acupuncture was as good as placebo, then it was appropriate to send clients to a “trained acupuncturist”. Since anyone can put on a white coat and stick needles absolutely anywhere, the only training required would be around not puncturing internal organs (something that happens with “trained” acupuncturists on occasion anyway).
At this moment in time we have over 3000 trials of acupuncture, and not one shows any benefit (not counting spurious trials which have been completely debunked as badly-designed rubbish). Without exception they state, “more research is needed”. 3000 trials and no results. Time to give it up.
I should also explain that the majority of these trials are done in China, with academics proven to commit fraud in order to get published in a Western journal.
67– Rubinstein S, et al. Spinal manipulative therapy for acute low back pain: an update of the Cochrane review.Spine (Phila Pa 1976). 2013 Feb 1;38(3):E158-77.
This latest Cochrane Review Update added 26 research studies involving over 2600 patients to the studies previously reviewed. Spinal manipulative therapy (SMT, i.e. chiropractic) was compared with fake chiropractic, other inert placebo therapies, and other therapies thought to be beneficial for acute lower back pain as both the primary and an added (adjunct) therapy.
The review concluded:“SMT is no more effective for acute low back pain than inert interventions, sham SMT or as adjunct therapy.”
As a result, classification of chiropractic has been downgraded from an already-low “clinically insignificant” to “non-existent effects”. While you will see studies claiming statistical significance of outcomes, these are so minuscule as to be of zero benefit to clients. (Statistical significance is not the same as clinical significance.)
68– Liu, X, et al. Which supplements can I recommend to my osteoarthritis patients? Rheumatology (Oxford). 2018 May 1;57(suppl_4):iv75-iv87.
Supplementation is of no benefit, and can be harmful. This massive meta-analysis examined a wide range of commonly-recommended supplements (glucosamine and many others) and found none effective for pain. In fact less than 2% of patients experienced even 20% improvement in symptoms. In addition adverse reactions were similar in all groups. Recommending supplements could be seen as wasting the time, energy, money, and hope, of chronic pain patients. In the case of curcumin, this is actually contra-indicated for people on certain medications, in particular the statins.
Further on curcumin, if indeed it can significantly reduce inflammation (which is a claim without robust evidence) then it could have a negative effect on the immune system and the ability to heal from injury. If we had no inflammation, we’d die. Inflammation is a critical function and we shouldn’t be trying to reduce it unless pathology indicates that we should.
69– Hasset, A, et al. The risk of suicide mortality in chronic pain patients. Curr Pain Headache Rep.2014;18(8):436.
Increased risk of suicide deaths amongst chronic pain sufferers.
70– Fishbain, D, et al. Suicide of chronic pain sufferers: Completed suicide in chronic pain. The Clinical Journal of Pain[01 Mar 1991, 7(1):29-36]
Statistics on completed suicide attempts amongst chronic pain sufferers. Keep in mind this was 1991, and there are anecdotal reports of increased rates of suicide since the abrupt stoppage of opioid medication in the absence of effective alternative treatment strategies.
71– Al-Shammari, M, et al. Legal marijuana use linked to more dependency, persistent vomiting. Clin Gastroenterol Hepatol. July 13, 2017.
Cannabis linked to increased nausea. Whilst there are plenty of anecdotes around improvement of nausea, and some clinical evidence, it is not yet robust, and there are strong indications that it can make nausea worse.
72– Perucca, E. Cannabinoids in the Treatment of Epilepsy: Hard Evidence at Last? J Epilepsy Res. 2017 Dec; 7(2): 61–76.
Cannabis linked to increased seizure rate. This extremely comprehensive and pro-cannabis study actually concluded by saying “we are very near to having evidence” (another way of saying “we do not yet have evidence”) that some cannabis preparations can help with seizures. This may be true, I hope it is, but it is still not yet proven, and the possibility of increased seizures is also still on the table, as described in this paper.
73– Andresen, S, et al. Ultramicronized palmitoylethanolamide in spinal cord injury neuropathic pain: a randomized, double-blind, placebo-controlled trial. Pain.2016 Sep;157(9):2097-103.
This study can be classified as robust because it is actually a RCT. It did however use PEA as an add-on therapy rather than comparing it with other treatment. Normally this would produce some seeming benefit (because “something” usually performs better than “nothing”, even if the “something” is a placebo treatment) but in this case it did not. PEA failed.
74– Neugebauer, V. The amygdala: different pains, different mechanisms. Pain. 2007 Jan; 127(1-2): 1–2.
Modulation of chronic pain via the amygdala. This is a fascinating and important paper, which describes the history of our understanding of acute vs chronic pain, and details changes in the amygdala region of the brain associated with development of chronic pain. I regard this as another piece of the puzzle in understanding non-nociceptive pain.
75– Williams, A, Rhudy, J. The influence of conditioned fear on human pain thresholds: Does preparedness play a role? J Pain 2007;8(7):598–606.
The researchers “… expected that classical conditioning would lead to fear, and that that fear would cause a drop in pain threshold. However, an alternative possibility is that such a drop in pain threshold might not be reliant on fear, but could be the direct effect of the classical conditioning procedure. In other words, it is plausible to suggest that pain might become a classically conditioned response, one that is driven not by nociception, but by non-nociceptive input that has been previously associated with nociception.”
76– Bonin, R, De Koninck , Y. A spinal analog of memory reconsolidation enables reversal of hyperalgesia. Nature Neurosciencevolume 17, pages1043–1045 (2014).
This is a scientific exposition of De Koninck’s “Recall and Erase” and it precisely mirrors our theory of chronic pain. Our point of difference is two-fold. Firstly we do not need to inject any chemical into the brain in order to extinguish the learned response, and secondly the sets of conditioned responses at play in chronic pain presentation are frequently highly-complex and can encompass virtually every aspect of a client’s life.
77– Taylor, A, Roger-Kerry. When Chronic Pain Is Not “Chronic Pain”: Lessons From 3 Decades of Pain. Journal of Orthopaedic & Sports Physical Therapy,2017, Volume:47 Issue:8 Pages:515-517
Article in Journal of Orthopaedic & Sports Physical Therapy. One case of misdiagnosis of sciatica for 30 years. Turned out to be a narrowed artery which required surgical intervention.
78– Peterson, K, Peterson, C. A case series evaluating the accuracy of manual muscle testing for predicting fetal sex. J Chiropr Med. 2012 Mar; 11(1): 1–6.
Plenty of studies show that when tested material is already known, manual muscle testing is fairly accurate (but not perfect, strangely). However as this study shows, when the information sought is unconscious, manual muscle testing is no better than chance.
79– Fritz, J, Childs, J, Wainner, R, Flynn, T. Primary care referral of patients with low back pain to physical therapy: impact on future health care utilization and costs. Spine (Phila Pa 1976).2012 Dec.
Only 7% of patients with low back pain are referred to physical therapy. This is not necessarily a bad thing because the evidence is that for chronic low back pain, physiotherapy is no better than doing exercises, and is not as beneficial as taking up an active hobby.
80– Placebo – Myths and Misconceptions – https://www.painscience.com/microblog/key-concepts-about-placebo-i-wish-every-reader-understood.html
Please understand that “placebo” is not actually a thing. It is merely a subjective perception which does not have any impact whatsoever on physical function. The only reason it is used in clinical trials is to test that a particular treatment is better than nothing. If the treatment provides a result that is less than, or approximately, placebo, it is rejected as worthless.
So the real meaning of placebo is “worthless”.
81– Madden, V, et al. Can Pain or Hyperalgesia Be a Classically Conditioned Response in Humans? A Systematic Review and Meta-Analysis. Pain Medicine, Volume 17, Issue 6, 1 June 2016, Pages 1094–1111
Over the past several years there has been increased curiosity amongst researchers over the role of conditioning in the development of many types of chronic pain. Unfortunately much of the research has focussed on using the artefact of conditioned pain modulation on healthy subjects and as probably should have been expected, this has produced inconclusive results.
In a large number of studies attempting to test the potential for conditioned stimuli to elicit or heighten the pain response, always using young healthy subjects (ie, using people who were probably not prone to developing chronic pain in any case) we see that well over 80% of subjects experienced pain or increased pain.
To my knowledge, our own research is the only attempt to date to conduct a trial with actual chronic pain patients and use extinction techniques to eliminate or reduce pain.
82– Barral, J, Croibier, A. Vagus nerve. Manual Therapy for the Cranial Nerves, 2009.
This paper provides a good overview of the vagus nerve.
83– Breit, S, Kupferberg, A, Rogler, G, Hasler, G. Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders. Front Psychiatry. 2018; 9: 44.
This paper demonstrates utility of vagus nerve stimulation in specific disorders.
84– Porges, S. The polyvagal theory: New insights into adaptive reactions of the autonomic nervous system. Cleve Clin J Med. 2009 Apr; 76(Suppl 2): S86–S90.
Professor Stephen Porges referred to the whole of the vagus nerve as the “polyvagal system” and has identified important functionality which others have claimed is evidence of a third nervous system, the “social engagement system”. It makes for very interesting reading but unfortunately has led to a lot of quackery.
85– O’Reardon, J, Cristancho, P, Peshek, A. Vagus Nerve Stimulation (VNS) and Treatment of Depression: To the Brainstem and Beyond Psychiatry (Edgmont). 2006 May; 3(5): 54–63.
There are several papers of this nature, demonstrating potential for vagus nerve stimulation to be utilised in the treatment of non-responsive depression. However the results have been rather modest, not surprising given that without an effective therapeutic landscape it might seem like a drop in a bucket. Also it required costly and risky neurological surgery.
There was a paper which came out of China (I’m not going to even bother citing it because at this stage I doubt anything coming out of China) which demonstrated that a non-invasive method of clipping electrodes to the ears was more effective than sham.
I favour mechanical stimulation of areas which are richly innervated by the vagus nerve. Non-invasive, completely free of cost, and completely portable (no equipment required) This is not because there is anything magical about the vagus nerve, it’s merely about getting a sufficiently intense sensory disruptive factor to apply simultaneously to an identified conditioned stimulus in order to extinguish a maladaptive conditioned response.
86– Hannibal, K, Bishop, M. Chronic Stress, Cortisol Dysfunction, and Pain: A Psychoneuroendocrine Rationale for Stress Management in Pain Rehabilitation. Phys Ther. 2014 Dec; 94(12): 1816–1825.
This paper explains the physiology of stress, including its impact on pain signalling and perception.