A novel paradigm to evaluate conditioned pain modulation in fibromyalgia

Abstract

Introduction: Application of noxious stimulation to one body area reduces pain sensitivity in a remote body area through activation of an endogenous pain-inhibitory network, a behavioral phenomenon referred to as conditioned pain modulation (CPM). The efficiency of CPM is predictive of a variety of health outcomes, while impaired CPM has been associated with various chronic pain conditions. Current methods used to assess CPM vary widely, and interest in CPM method development remains strong. Here, we evaluated a novel method for assessing CPM in healthy controls and fibromyalgia (FM) patients using thumb pressure as both a test and conditioning stimulus.

Methods: Sixteen female FM patients and 14 matched healthy controls underwent CPM testing with thumbnail pressure as the test stimulus, and either cold water or noxious pressure as the conditioning stimulus. CPM magnitude was evaluated as the difference in pain rating of the test stimulus applied before and during the conditioning stimulus.

Results: In healthy controls, application of either pressure or cold water conditioning stimulation induced CPM as evidenced by a significant reduction in test stimulus pain rating during conditioning (P=0.007 and P=0.021, respectively). In contrast, in FM patients, neither conditioning stimulus induced a significant CPM effect (P>0.274). There was a significant difference in CPM magnitude for FM patients compared to healthy controls with noxious pressure conditioning stimulation (P=0.023); however, no significant difference in CPM was found between groups using cold water as a conditioning stimulus (P=0.269).

Conclusion: The current study demonstrates that thumbnail pressure can be used as both a test and conditioning stimulus in the assessment of CPM. This study further confirms previous findings of attenuated CPM in FM patients compared with healthy controls.

Keywords: cold pressor test; diffuse noxious inhibitory controls; pressure pain; quantitative sensory testing.

Figure 1

CPM paradigm. Notes: Individually predetermined pain-60 test pressure was applied to the nondominant thumbnail for 30 seconds at baseline. After a 5 minute rest, the conditioning stimulus (either a pain-60 pressure to the dominant thumbnail or immersion of the dominant hand in a 12°C water bath) was applied for 60 seconds. For the last 30 seconds of the conditioning stimulus, the original test stimulus was reapplied to the nondominant thumbnail. Abbreviations: CPM, conditioned pain modulation; min, minutes; R, time point at which subjects rated the test stimulus; Sec, seconds.

Figure 2

Changes in pain ratings in HC and FM patients during a CPM paradigm. Notes: CPM was assessed by using pressure pain applied to the nondominant left thumbnail as the test stimulus and either pressure pain to the contralateral thumbnail (A) or cold water immersion of the contralateral hand (B) as the conditioning stimulus. Decreases in test stimulus pain ratings during conditioning stimulation are an indication of intact CPM. Note that not all healthy controls exhibited CPM and not all FM patients exhibited a lack of CPM. (C) Pain ratings (mean ± SD) at baseline and during CPM are shown by group and stimulus. Differences in test stimulus ratings before and during CPM were assessed with paired-samples t-tests. In healthy controls, the mean pain rating of the test stimulus significantly decreased when either pressure pain (n=7) or cold water (n=12) was used as the conditioning stimulus. In FM patients, the mean pain rating did not significantly change regardless of conditioning stimulus used (pressure pain, n=8; cold water, n=10). A subset of subjects (n=7) underwent both test stimuli on separate visits. Abbreviations: CPM, conditioned pain modulation; FM, fibromyalgia; HC, healthy control; SD, standard deviation.