Endogenous analgesic effect of pregabalin: A double‐blind and randomized controlled trial

Abstract

Background: Conditioned pain modulation (CPM) is widely used to measure endogenous analgesia, and a recent study indicated that drugs that act on endogenous analgesia are more effective in individuals with lower CPM. Recent animal studies have indicated that pregabalin activates endogenous analgesia by stimulating the descending pain inhibitory system. The present study examined whether the analgesic effect of pregabalin is greater in individuals with lower original endogenous analgesia using CPM. Methods: Fifty-nine healthy subjects were randomly assigned to either a pregabalin group or a placebo group, and 50 of them completed the study. CPM was measured before and after pregabalin or placebo administration. The correlation of initial CPM to change in CPM was compared between the pregabalin and placebo groups. Results: Initial CPM was significantly correlated with the change in CPM in the pregabalin group (r = À0.73, p < 0.0001) but not in the placebo group (p = 0.56) (difference in correlation coefficients between groups; p = 0.004). Furthermore, the initial CPM significantly affected the change in CPM in the pregabalin group but not in the placebo group (pregabalin group: adj R 2 = 0.51, p < 0.001, y = À0.54x + 2.98; placebo group: p = 0.56, significant difference in regression slopes; p = 0.015). These results indicate that pregabalin has a higher endogenous analgesic effect in individuals with lower original endogenous analgesia. Significance: The analgesic effect of pregabalin depends on the original endogenous analgesia status. Its effect on conditioned pain modulation (CPM) was stronger for subjects with lower original endogenous analgesia, suggesting that the mechanism of pregabalin involves the improvement of endogenous analgesia.

Systematic review with meta‐analysis: conditioned pain modulation in patients with the irritable bowel syndrome

“…Sugimine et al explored the effect of Pregabalin on conditioned pain modulation in a placebo controlled study . There was a clear correlation between baseline conditioned pain modulation and that after receiving Pregabalin ( r = 0.73, P < 0.0001).…”

“…Recent evidence suggests that assessment of conditioned pain modulation may allow for the individualisation of pain treatments in other conditions of chronic pain; for example, Wilder-Smith et al and Landau etal showed that baseline conditioned pain modulation may predict postsurgical neuropathic pain [48][49][50][51][52]. Sugimine et al explored the effect of Pregabalin on conditioned pain modulation in a placebo controlled study 53. There was a clear correlation between baseline conditioned pain modulation and that after receiving Pregabalin (r = 0.73, P < 0.0001).…”

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

“…Pregabalin, a GABAergic medication used to treat neuropathic pain and fibromyalgia among other conditions, may also produce its analgesic effect by enhancing CPM. Importantly, pregabalin efficacy is influenced by initial CPM efficacy, such that individuals with less efficient CPM benefit more from the drug (Sugimine, Saito, Araki, Yamamoto, & Obata, 2017). …”

Effectiveness and Adverse Events of Gabapentinoids as Analgesics for Patients with Burn Injuries: A Systematic Review with Meta-Analysis and Trial Sequential Analysis

“…The latest guidelines for acute burn pain from the American Burn Association in 2020 suggest the adjunctive use of gabapentinoids for refractory burn pain and neuropathic pain, based on only two RCTs and three non-RCTs [2]. To provide updated and evidence-based recommendations, we included five RCTs in our systematic review and excluded studies if burn pain was elicited by experimental models, such as thermodes or intradermal capsaicin [24,25]. All of the included trials on the adult population applied baseline analgesics using morphine with or without other adjunctive medication.…”