What is central sensitisation? A dummies’ guide to what it is and why might exercise help

This is a supplementary blog and dummies’ guide to a paper first published online in the BJSM in 2018. Smith BE, Hendrick P, Bateman M, et al. Musculoskeletal pain and exercise—challenging existing paradigms and introducing new British Journal of Sports Medicine 2019;53:907-912.

It formed part of a chapter in my recent PhD that looked at the assessment and management of patellofemoral pain. As such, my work is a product of supervision and collaboration.  So I would like to start by acknowledging and thanking my supervisors Pip Logan and Paul Hendrick, and collaborators Marcus BatemanSinead HoldenChris LittlewoodFiona MoffattMichael Rathleff, James Selfe and Toby Smith.

Introduction

Central sensitisation is a common phrase – used both clinically and in research. But what does it actually mean? Moreover, how do we measure it?

Within the research world, it typically means increased responsiveness of nociceptive neurons to normal input (i.e. touch and heat) [1].

It can be further explained that the way the nerves work in the central nervous system changes over time. Meaning that pain is no longer directly related to the presence and intensity of harmful or unpleasant sensations [2,3].

There is no direct way of measuring central sensitisation. However, there are substitute measurements which are thought to represent central sensitisation. These include:

  1. Hyperalgesia
  2. Allodynia
  3. Temporal summation of pain (TSP)
  4. Diffuse noxious inhibitory control (DNIC) [1–4].

Hyperalgesia

Hyperalgesia is an increased pain sensitivity.  More specifically, it means an increased pain response to normally painful stimuli [5].

For example. If someone were to experience a pinprick to their ankle, they might score the pain one out of 10, for example. However, if they currently had an inflamed and swollen ankle from an acute ankle sprain, they would likely be experiencing hyperalgesia. In this scenario, the same pinprick would result in a more painful response and a higher pain score being recorded.

The process by which it happens is unclear. However, it is thought to occur in the neurotransmitters and receptors on the postsynaptic membrane*; likely involving glutamate, growth factors, cytokines and chemokines [2]. This process produces an increase in responsiveness and a heightened sensitivity to inputs [2].  Further details on this process can be read in our paper Musculoskeletal pain and exercise—challenging existing paradigms and introducing new British Journal of Sports Medicine 2019;53:907-912, or I suggest a good read of The Routledge Handbook of Philosophy of Pain.

*the postsynaptic membrane is the membrane in a nerve synapse that receives a signal (neurotransmitter) from the presynaptic cell.

Allodynia

Allodynia, by contrast, is a pain response to a stimulus that is not normally painful [3,5].

An example of allodynia is the person who is suffering from persistent low back pain who complains of increased pain when they are hugged.

The exact mechanisms are widely contested, and no one really knows. However, it is thought that structural alterations occur in the dorsal horn of the spinal cord so that non-noxious thermal, mechanical or joint movement inputs can contribute to the pain experience [2,3,6]. More reading here Musculoskeletal pain and exercise—challenging existing paradigms and introducing new British Journal of Sports Medicine 2019;53:907-912, or here.

Temporal summation of pain (TSP)

Temporal summation of pain is an increasing level of pain felt, with the repeated stimulus of the same intensity.

For example, a patient with chronic knee pain performing knee exercises may complain of increasing levels of pain, the more repetitions of the same exercise they perform, which could be attributed to TSP.

A variety of stimuli can be used to assess TSP, including, heat, cold, pressure and electrical. In clinical studies, TSP has been shown to be present in patients with osteoarthritis [4].

More reading here Musculoskeletal pain and exercise—challenging existing paradigms and introducing new British Journal of Sports Medicine 2019;53:907-912.

Diffuse noxious inhibitory control (DNIC)

Another commonly assessed pain mechanism in MSK pain research is the diffuse noxious inhibitory control paradigm [4]. It describes the descending endogenous pain modulation system, covering a few overlapping mechanisms that can alter and reduce pain perception [7]. The two primary mechanisms are the activation of descending nociceptive inhibitory mechanisms [8]; and the release of endogenous opioids [9].

An example of this in action is when one might report lower pain scores for a primary complaint, say low back pain, in the presence of a painful secondary stimulus, for instance placing the hand in ice-cold water.

The descending inhibitory system involves a few areas of the brain, most notably the periaqueductal gray [10,11]. The periaqueductal gray interacts with other brain regions, including the amygdala and hypothalamus, which in turn have multi-direction connections to the dorsal horn of the spinal cord. Here it synapses onto neurons that work in the opposite direction to nociceptive signalling, reducing pain perception [12].

Diffuse noxious inhibitory control is assessed through the conditioned pain modulation response (also known as “pain inhibits pain”) [13]. During conditioned pain modulation, the descending pain inhibitory responses are activated during a painful stimulus. This is used as a substitute for the overall effectiveness of the endogenous analgesic system, likely occurring through both the opioid and non-opioid pathways. It results in a decrease in the excitability of neurons, a decrease in neurone firing rates, and inhibition of neurotransmitters, contributing to anti-nociception, or a reduction of the pain perception [14].

Impairments in conditioned pain modulation have been shown in long-standing pain conditions such as osteoarthritis [15].

Summary—Pain Science 2018 in a nutshell. From Musculoskeletal pain and exercise—challenging existing paradigms and introducing new British Journal of Sports Medicine 2019;53:907-912.

How might exercise help?

People with persistent MSK pain may have changes to the way their central nervous system processes pain and exercise is often a common form of therapy. But how might if help?

It is well understood that an acute bout of exercise can result in analgesia (pain relief), and this phenomenon is termed exercise-induced hypoalgesia (EIH). It is thought another form of the endogenous pain modulatory processes [16].

timelapse photography of a person riding a road bike

Evidence for this analgesic effect of exercise comes from experimental studies that demonstrated a reduction in pain sensitivity (usually measured by pressure pain thresholds, and temporal summation of pain) after exercise [1,15,17]. Several different exercise interventions have been investigated, including cardiovascular exercise (running and cycling) and resistance exercise, including isometric and dynamic resistance [16].

For example, Naugle et al. 2012 [16] systematic review attempted to examine the effects of acute exercise on pain perception in healthy adults and adults with chronic pain using meta-analytic techniques. Studies that used repeated measured of pain threshold and pain intensity with acute isometric, aerobic, or dynamic resistance exercise in pain-free individuals and those with persistent pain were included. They concluded that exercise reduced pain with experimentally induced pain in healthy participants, with effects ranging from small to large. And for those with persistent pain, they also concluded that exercise reduced pain perception, however, with highly variable results.

It is thought the endogenous opioid system is triggered by exercise-induced activation of arterial baroreceptors following increases in heart rate and blood pressure [18–20]. It is thought to involve a release of β-endorphins from the pituitary and hypothalamus, and µ-opioid receptors [21].

Another possible reason exercises may work to reduce pain is through the conditioned pain modulation response.  As previously explained, during conditioned pain modulation, the descending pain inhibitory responses are challenged during a painful conditioning stimulus [14]. Studies have demonstrated that pain-related fear negatively disrupts the endogenous pain inhibitory systems via the process of conditioned pain modulation, for example, higher levels of catastrophising during experimental studies, was strongly associated with lower activation of the diffuse noxious inhibitory control and higher pain ratings [22]. The network of subcortical and cortical structures associated with diffuse noxious inhibitory control and conditioned pain modulation include the amygdala [23]. Exercises could provide the painful conditioning stimulus needed to trigger the conditioned pain modulation response and activity of the amygdala, which may provide a mechanistic rationale for improvements in pain and function. More reading here Musculoskeletal pain and exercise—challenging existing paradigms and introducing new British Journal of Sports Medicine 2019;53:907-912.

Found this blog useful? Want to learn a contemporary, evidenced-based approach to the assessment and management of patellofemoral pain? Have a look at available course dates and information. tile

Summary

I hope you’ve found this dummies’ guide to central sensitisation and principles of general exercise for central sensitisation helpful.

The next two supplementary blogs in this series will cover the role of the immune system and affective aspects of pain. Keep an eye out for them.

References

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[2]         Thacker M, Moseley L. Pathophysiological Mechanisms of Chronic Pain. In: Corns J, editor. Routledge Handb. Philos. Pain, Routledge; 1 edition; 2017, p. 124–39.

[3]         Sandkühler J. Models and mechanisms of hyperalgesia and allodynia. Physiol Rev 2009;89:707–58.

[4]         Le Bars D, Dickenson AH, Besson J-M. Diffuse noxious inhibitory controls (DNIC). I. Effects on dorsal horn convergent neurones in the rat. Pain 1979;6:283–304.

[5]         Merskey H, Bogduk N. IASP taxonomy. Updat from Pain Terms, A Curr List with Defin Notes Usage” (Pp 209-214) Classif Chronic Pain, Second Ed IASP Task Force Taxon 2012.

[6]         Jensen TS, Finnerup NB. Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. Lancet Neurol 2014;13:924–35.

[7]         Yarnitsky D. Role of endogenous pain modulation in chronic pain mechanisms and treatment. Pain 2015;156:S24–31.

[8]         Ray CA, Carter JR. Central modulation of exercise-induced muscle pain in humans. J Physiol 2007;585:287–94.

[9]         Koltyn KF, Arbogast RW. Perception of pain after resistance exercise. Br J Sports Med 1998;32:20–4.

[10]      Ossipov MH, Dussor GO, Porreca F. Central modulation of pain. J Clin Invest 2010;120:3779.

[11]      Heinricher MM, Fields HL. Central nervous system mechanisms of pain modulation. Wall Melzack’s Textb. pain, Elsevier Health Sciences, Philadelphia; 2013, p. 129–42.

[12]      Geuter S, Koban L, Wager TD. The cognitive neuroscience of Placebo Effects: concepts, predictions, and Physiology. Annu Rev Neurosci 2017.

[13]      Stuckey HL. Methodological issues in social health and diabetes research. J Soc Heal Diabetes 2014;2:6–8.

[14]      Kapitzke D, Vetter I, Cabot PJ. Endogenous opioid analgesia in peripheral tissues and the clinical implications for pain control. Ther Clin Risk Manag 2005;1:279.

[15]      Lewis GN, Rice DA, McNair PJ. Conditioned pain modulation in populations with chronic pain: a systematic review and meta-analysis. J Pain 2012;13:936–44.

[16]      Naugle KM, Fillingim RB, Riley JL. A meta-analytic review of the hypoalgesic effects of exercise. J Pain 2012;13:1139–50.

[17]      Koltyn KF, Brellenthin AG, Cook DB, Sehgal N, Hillard C. Mechanisms of exercise-induced hypoalgesia. J Pain 2014;15:1294–304.

[18]      Koltyn KF, Umeda M. Exercise, hypoalgesia and blood pressure. Sport Med 2006;36:207–14.

[19]      Ghione S. Hypertension-associated hypalgesia. Hypertension 1996;28:494–504.

[20]      Nijs J, Kosek E, Vanoosterwijck J, Meeus M, Oosterwijck J Van, Van Oosterwijck J. Dysfunctional endogenous analgesia during exercise in patients with chronic pain: to exercise or not to exercise? Pain Physician 2012;15:ES205-13.

[21]      Bender T, Nagy G, Barna I, Tefner I, Kádas É, Géher P. The effect of physical therapy on beta-endorphin levels. Eur J Appl Physiol 2007;100:371–82.

[22]      Goodin BR, McGuire L, Allshouse M, Stapleton L, Haythornthwaite JA, Burns N, et al. Associations between catastrophizing and endogenous pain-inhibitory processes: sex differences. J Pain 2009;10:180–90.

[23]      Wilder-Smith CH, Schindler D, Lovblad K, Redmond SM, Nirkko A. Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controls. Gut 2004;53:1595–601.