The journal of pain : official journal of the American Pain Society
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Review Meta Analysis
Towards Identifying Moderators of Associations Between Pre-Surgery Emotional Distress and Post-Operative Pain Outcomes: A Meta-Analysis of Longitudinal Studies.
Presurgery emotional distress has had variable associations with outcomes of surgery in past narrative reviews. This meta-analysis was designed to evaluate the overall strengths of relations between presurgical emotional distress and key postsurgical pain outcomes (ie, pain intensity, analgesic use, functional impairment) and to identify moderators that might explain effect size heterogeneity between studies. PubMed, Web of Science, PsychINFO, Google Scholar, and Science Direct databases were searched to identify studies subjected to meta-analysis. Forty-seven studies of 6,207 patients met all 10 inclusion criteria. High presurgery emotional distress levels were associated with significantly more postsurgical pain, analgesic use, and impairment after surgery, with small to medium average effect sizes. Moderator analyses for relations between distress and pain intensity indicated effect sizes were larger in studies that assessed catastrophizing, anxiety, and/or depression than other types of emotional distress as well as those with lower rather than higher quality scores. Associations between presurgery distress and postoperative impairment were moderated by type of surgery. Heterogeneity in these relations was reduced or no longer significant after statistically controlling for moderators. Moderator analyses also supported the role of presurgery emotional distress as a risk factor for, rather than simply a correlate of, elevations in postoperative pain and disability. ⋯ This meta-analysis indicates presurgery emotional distress has significant associations with postoperative outcomes but specific methodological factors and sample characteristics contribute to effect size variability in the literature. Considering emotional distress within presurgical assessment protocols may aid in identifying vulnerable patients who can benefit from interventions targeting distress reductions.
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The transient receptor potential cation channel subfamily M 8 (TRPM8) agonist L-menthol has been used traditionally for its topical counterirritant properties. Although the use of topical L-menthol for pain is casuistically established, evidence regarding its efficacy is negligible. This study aimed to characterize the effect of L-menthol as a counterirritant on cutaneous pain and hyperalgesia provoked by topical application of the transient receptor potential cation channel, subfamily A, member 1 (TRPA1) agonist trans-cinnamaldehyde (CA). In a randomized, double-blinded study CA was applied to a 3 × 3-cm area of the volar forearm evoking neurogenic inflammation, pain, mechanical, and thermal hyperalgesia in 14 healthy volunteers. In different sessions, 10% CA alone or 40% L-menthol applied simultaneously with 10% CA were administered for 20 minutes, throughout which the subjects rated the pain intensity on a visual analogue scale of 0 to 10. Extensive quantitative sensory testing was conducted and superficial blood flow (neurogenic inflammation) was recorded. Administration of CA evoked spontaneous pain, neurogenic inflammation, thermal hyperalgesia, and primary and secondary mechanical hyperalgesia. Coadministration of topical L-menthol reduced spontaneous pain intensity (P < .01), neurogenic inflammation (P < .01), primary mechanical hyperalgesia (P < .05), secondary mechanical hyperalgesia (P < .05), and heat hyperalgesia (P < .05), but not cold hyperalgesia. L-menthol exhibited inhibitory effects on simultaneously established pain, hypersensitivity, and neurogenic inflammation in a human TRPA1-induced pain model. Potent TRPM8 agonists could be useful as topical antihyperalgesics. The study and the trial protocol is registered and approved by the local research ethics committee under the jurisdiction of the Danish Medicines Agency number N-20130005. The protocol also is registered at Clinicaltrials.gov under NCT02653703. ⋯ Drugs interacting with transient receptor potential channels are of great therapeutic potential. In the present study we established cutaneous pain and hyperalgesia using the TRPA1 agonist CA. Subsequently, we showed that the frequently used topical counterirritant and TRPM8 agonist, L-menthol, decreased evoked pain, hyperalgesia, and inflammation, indicating direct and indirect antinociceptive mechanisms.