Training Endogenous Pain Modulation: A Preliminary Investigation of Neural Adaptation Following Repeated Exposure to Clinically-relevant Pain

BACKGROUND & OBJECTIVE

Pain can change. What is happening cortically when it does? What is a helpful course of action for clinicians to support a change in pain? This study investigated the effect of repeated exposure to pain on the ability of an individual to modulate the pain response.

There three main goals of this study were to:

1. assess the role of the nucleus accumbens-medial prefrontal cortex (NAc-mPFC) pathway in pain adaptation
2. evaluate the effects of repeated exposure to musculoskeletal pain on the connectivity among specific pain-related brain regions and networks
3. evaluate associations among changes in neural dynamics, quantitative sensory testing (QST), and self-reported pain experience (1)

Opioids have failed to relieve chronic pain. In fact, long term use may impair the ability to modulate pain, making the person more sensitive (2). The authors of this study stated that analgesic treatments have reduced endogenous pain modulatory capacity (PMC). They propose that efforts to increase PMC should increase resilience to subsequent pain-provoking events (3). Research into successful regulation of pain modulation indicates a correlation to the connectivity of the NAc-mPFC.

Clinicians can take this interesting paper as a step towards understanding how we can aim to improve pain modulation capabilities as a target of treatment, instead of aiming for pain reduction itself.

METHODS

Participants were randomized into two groups. The control group had one exposure to a delayed onset muscle soreness (DOMS) inducing activity and was tracked with qualitative sensory testing (QST) and fMRI. The research group was exposed to DOMS repeatedly (daily) as well as QST and fMRI. The study duration for both groups was approximately 40 days.

Both groups were without caffeine, alcohol, medication, and other treatment such as massage or stretching during the study period. This rigorous exclusion criteria set out to minimize variability of subject’s ability to affect pain perception.

The research group completed 5 sessions. The pain experience was qualified using a pain experience visual analog scale (PEVAS) that included depression, anxiety, frustration, fear, anger, unpleasantness, and pain intensity. Pain with movement was rated using the VAS following elbow flexion exercises. Ratings were taken on both spontaneous pain and pain with movement, tracking peak DOMS on each rated variable for analyses.

RESULTS

Age, sex, racial, and ethnic composition was similar across the groups. The repeated DOMS group had significant decreases in post-DOMS pain and in the thermal quantitative sensory testing. There was also increased adaptation compared to the control group in the cortical structures. Specific changes were seen in the NAc-mPFC, in the frontal cortex, and in connectivity among the sensory motor and pre-frontal cortices. The authors suggest these changes correlate with the reduction in post-DOMS distress.

LIMITATIONS

Is it the repeated exposure, or the learning that occurs from the exposure, or changes in the physical properties of the muscles that explains these results? The authors acknowledge that there would need to be another group that did not experience DOMS in order to clarify this. Furthermore, the authors clarify that this is a novel perspective, to practice purposeful exposure and recovery to musculoskeletal (MSK) pain in order to improve PMC. Finally, the relatively small number of participants in the study combined with the inherent imprecision of imaging limits the breadth of conclusions we can make towards clinical practice at this stage.

CLINICAL IMPLICATIONS

This study supports purposefully provoking DOMS in order to invoke change not only in the MSK structures, but also in the cortical regions that modulate pain. This is a clinically relevant study, giving support to increasing the demand and challenge of therapy at sufficient intensity to help modulate pain.

Exposure, recovery, and repetition are classic components of MSK rehabilitation. Advancing exercises sufficiently to create DOMS and recovery opportunities is not yet common practice in the treatment of chronic and persistent pain. Some take an opposite route of avoiding MSK pain or seeing DOMS as an indication that the program is overloaded. Others think DOMS following therapy means that there must be something wrong (as opposed to reasonable soreness following adequate stress to MSK structures).

This paper proposes that it is safe (and helpful) to provide resistance sufficient to provoke DOMS (that a person is able to adapt to), increasing their ability to modulate the pain response through increased cortical mechanisms. Clinicians can take this interesting paper as a step towards understanding how we can aim to improve pain modulation capabilities as a target of treatment, instead of aiming for pain reduction itself. An added bonus to this approach is that resistance training is well suited for optimizing independence and self-efficacy, the ultimate aim of rehabilitation.

+STUDY REFERENCE

Sevel L, Boissoneault J, Alappattu M, Bishop M and Robinson M (2019) Training endogenous pain modulation: a preliminary investigation of neural adaptation following repeated exposure to clinically-relevant pain. Brain Imaging and Behavior.

SUPPORTING REFERENCE

1. Sevel, L., Boissoneault, J., Alappattu, M., Bishop, M. and Robinson, M. (2019). Training endogenous pain modulation: a preliminary investigation of neural adaptation following repeated exposure to clinically-relevant pain. Brain Imaging and Behavior.
2. Rivat, C. and Ballantyne, J. (2016). The dark side of opioids in pain management. PAIN Reports, 1(2), p.e570.
3. Seery, M. (2011). Challenge or threat? Cardiovascular indexes of resilience and vulnerability to potential stress in humans. Neuroscience & Biobehavioral Reviews, 35(7), pp.1603-1610.