Variability in conditioned pain modulation predicts response to NSAID treatment in patients with knee osteoarthritis

Abstract

BackgroundPatients with painful knee osteoarthritis (OA) demonstrate hyperalgesia and altered pain-modulatory responses. While some prior work has demonstrated cross-sectional associations between laboratory and clinical pain measures, it is unknown whether individual variability in quantitative sensory testing (QST) responses at baseline can prospectively predict analgesic treatment responses.MethodPatients with knee OA (n = 35) were compared on QST responses to a demographically-matched pain-free control group (n = 39), after which patients completed a month-long treatment study of diclofenac sodium topical gel (1 %), applied up to 4 times daily.ResultsOA patients demonstrated reduced pain thresholds at multiple anatomic sites, as well as reduced conditioned pain modulation (CPM) and enhanced temporal summation of pain. The most pain-sensitive patients tended to report the most intense and neuropathic OA pain. Following diclofenac treatment, the knee OA cohort showed a roughly 30 % improvement in pain, regardless of the presence or absence of neuropathic symptoms. Baseline CPM scores, an index of endogenous pain-inhibitory capacity, were prospectively associated with treatment-related changes in clinical pain. Specifically, participants with higher CPM at baseline (i.e., better functioning endogenous pain-inhibitory systems) showed more reduction in pain at the end of treatment (p < .05).ConclusionsThese results support prior findings of amplified pain sensitivity and reduced pain-inhibition in OA patients. Moreover, the moderate to strong associations between laboratory-based measures of pain sensitivity and indices of clinical pain highlight the clinical relevance of QST in this sample. Finally, the prospective association between CPM and diclofenac response suggests that QST-based phenotyping may have utility in explaining inter-patient variability in long-term analgesic treatment outcomes.Trial registrationClinicalTrials.Gov Identifier: NCT01383954. Registered June 22, 2011.

Pain Modulation: From Conditioned Pain Modulation to Placebo and Nocebo Effects in Experimental and Clinical Pain

“…The function of CPM mechanisms is sometimes preserved in rheumatoid arthritis (up to 5 years after diagnosis) (Leffler, Kosek, Lerndal, Nordmark, & Hansson, 2002) and in osteoarthritis (OA), but impaired in temporomandibular joint (TMJ) arthralgia patients (Kothari et al, 2016) at sites with chronic pain but not at pain-free sites (Oono et al, 2014). Knee OA has sometimes been associated with reduced CPM and enhanced temporal summation of pain (Edwards et al, 2016), which predicts less pain relief after total knee replacement (Petersen, Graven-Nielsen, Simonsen, Laursen, & Arendt-Nielsen, 2016). Even though OA patients might not report a pain reduction following painful CS (provoked OA pain), magneto-encephalography and electroencephalography techniques indicate a decreased activation of the cingulate gyrus (Quante, Hille, Schofer, Lorenz, & Hauck, 2008).…”

Quantitative sensory testing measures individual pain responses in emergency department patients

“…One study in surgical patients found QST measures, primarily lower electrical and heat pain thresholds, were associated with higher postoperative analgesic requirements 29. Recent studies suggest that QST measures can identify interindividual differences in particular mechanisms of pain perception, such as descending-inhibitory activity, which can explain responses to specific types of drugs 30,31. Our study demonstrates the feasibility of similarly measuring interindividual variation in ED patients.…”

The Potential Role of Sensory Testing, Skin Biopsy, and Functional Brain Imaging as Biomarkers in Chronic Pain Clinical Trials: IMMPACT Considerations

“…In another open-label pilot study, both enhanced central sensitization (i.e., pain hypersensitivity) assessed using QST and decreased CPM at baseline predicted lower pain intensity 3 months after implantation of a spinal cord stimulator [31]. In contrast to the inverse association between basal CPM function and analgesia in response to these central nervous-system focused treatments, a recent open-label study of topical diclofenac for knee OA patients indicated that more robust pre-treatment CPM predicted better analgesic responses to this peripherally-applied NSAID [49]. …”

“…Furthermore, we are aware of only a small number of studies supporting the use of sensory testing as a predictor of treatment response for non-neuropathic pain conditions. In addition to those previously described in FM [76] and OA [49], one pharmacologic trial in low back pain appears to be ongoing [168], and several exploratory studies in migraine have linked a phenotype of persistent mechanical allodynia with a reduced analgesic response to triptans [30, 109], but these await replication in controlled studies.…”