Descending Pain Modulation in Irritable Bowel Syndrome and Non-Specific Chronic Low Back Pain

Abstract

Descending modulatory circuits from the brain may inhibit or facilitate ascending nociceptive transmission. Changes in descending pain modulation profoundly influence pain perception. Neurophysiological measures of descending pain modulation have been developed and the most commonly performed approach is conditioned pain modulation (CPM). Aim: This investigation focused on whether descending pain modulation is altered in chronic pain using CPM in people with two distinctly different chronic pain conditions, irritable bowel syndrome (IBS) and non-specific chronic low back pain (CLBP). A broader examination of pain processing was also undertaken examining the associations between alterations in CPM, spinal sensitisation, somatic sensitivity, cognitions, mood states and behavioural patterns. Method: A case-control study (age and gender matched) compared descending pain modulation in a community sample with IBS (n=25), CLBP (n=25) and healthy controls without chronic pain or any current pain (n=25). Participants underwent quantitative sensory testing (QST) to assess large and small fibre sensory function across sites anatomically near to and distant from their primary pain (hand-C7, abdomen-LLQ, low back-L4 or posterior thigh-S2). Z score transformation was used to compare somatosensory thresholds between sites within each participant group. In addition, a CPM protocol was employed to assess descending pain modulation using the nociceptive spinal cord withdrawal reflex (NWR). The NWR was achieved by stimulating the sural nerve (at the ankle) and measuring the EMG potentials from the biceps femoris muscle (at the posterior thigh). After baseline measurements of the NWR, a cold conditioning stimulus (using a refrigerated bath) was applied to the left hand for 5 minutes. Reflex potential measurements as well as pain intensity ratings were taken during the 2nd and 5th minutes of immersion and 2nd minute post immersion. The association between these measures and psychological factors including pain-related self-efficacy (PSEQ) and pain catastrophising (PRSS), mood (depression, anxiety and stress, DASS21) and pain coping behaviour (active coping, PRSS) were evaluated using validated questionnaires. Results: There were no statistical differences between participants with IBS and CLBP and healthy controls in the average reduction in the NWR potential and pain intensity scores compared during and after cold stimulus conditioning. All groups demonstrated marked variability in response to CPM, displaying a mix of inhibitory, facilitatory and no response. In addition, QST responses did not detect local or wide-spread sensitivity in the two participant groups when compared to healthy controls. Mediation analyses revealed that changes in descending pain modulation (measured by CPM response) did not predict changes in anatomically local or distant sensory testing measures. Psychological factors were also not found to be significant moderators for CPM in this study population. Conclusion: Despite the prevailing reports from the current body of literature that descending inhibition of pain and somatosensory function are impaired in IBS and CLBP, no such difference was found in these participant cohorts with IBS and CLBP and healthy controls. While these results were contrary to the initial hypothesis, it is believed they may characterise those who are not seeking treatment, despite moderately severe chronic pain, and do not have major mood, cognitive or functional disturbances. The results also highlight methodological issues, particularly the variability of the CPM and QST measures and the inherent variation in individual pain modulation profiles. It is acknowledged that pain modulation is not confined to one descending circuit and as such CPM testing is likely to measure only one aspect of the descending pain modulatory system. It is highlighted that CPM examines an evoked response to a short-lived noxious stimulus and that care must be taken with conclusions made about the resting state of the descending modulatory system when examining results. Recommendations for future research on descending modulation employing the CPM paradigm include the use of both pain perception and a neurophysiological measure of nociception as outcome measures and ongoing efforts to define comparable protocols and methods to assess clinically relevant categories of CPM response.