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Opioids are frequently overprescribed after surgery. The 2018 American Urological Association position statement on opioid use suggests using the lowest dose and potency to achieve pain control, but a lack of procedure-specific prescribing guidelines contributes to wide variation in prescribing patterns. To address this gap, this study aims to develop opioid prescribing recommendations through an expert panel consensus.
Learn More >Transcutaneous electrical nerve stimulation (TENS) promotes antinociception by activating the descending pain modulation pathway and consequently releasing endogenous analgesic substances. In addition, recent studies have shown that the endocannabinoid system controls pain. Thus, the present study investigated the involvement of the endocannabinoid system in TENS-induced antinociception of cancer pain using a cancer pain model induced by intraplantar (i.pl.) injections of Ehrlich tumor cells in male Swiss mice. Low- and high-frequency TENS was applied for 20 min to the mice's paws, and to investigate the involvement of the endocannabinoid system were used the N-(peperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pitazole-3-carboixamide (AM251), a cannabinoid CB receptor antagonist and (5Z,8Z,11Z,14Z)-5,8,11,14-eicosatetraenyl-methylester phosphonofluoridic acid (MAFP), an inhibitor of the endocannabinoid metabolizing enzyme fatty acid amide hydrolase, injected by via i.pl., intrathecal (i.t.), and intra-dorsolateral periaqueductal gray matter (i.dl.PAG). Furthermore, liquid chromatography-tandem mass spectrometry, western blot, and immunofluorescence assays were used to evaluate the endocannabinoid anandamide (AEA) levels, cannabinoid CB receptor protein levels, and cannabinoid CB receptor immunoreactivity, respectively. Low- and high-frequency TENS reduced the mechanical allodynia induced by Ehrlich tumor cells and this effect was reversed by AM251 and potentiated by MAFP at the peripheral and central levels. In addition, TENS increased the AEA levels and the cannabinoid CB receptor protein levels and immunoreactivity in the paw, spinal cord, and dorsolateral PAG. These results suggest that low- and high-frequency TENS is effective in controlling cancer pain, and the endocannabinoid system is involved in this effect at both the peripheral and central levels. Perspective: TENS is a non-pharmacological strategy that may be used to control cancer pain. Identification of a new mechanism involved in its analgesic effect could lead to the development of clinical studies as well as an increase in its application, lessening the need for pharmacological treatments.
Learn More >Bone Morphogenetic Protein-2/4 (BMP2/4) have been recognized as promoters of astrocyte activity. Substantial evidence suggests BMP2/4 may be elevated and play a critical role in astrocyte activation upon spinal cord injury. Although neuropathic pain (NP) is similarly associated with astrocyte activation, the participation of BMP2/4 in this regard still remains unclear. A rat model of NP achieved by spinal nerve ligation (SNL) at L5 was used to evaluate the expression of glial fibrillary acidic protein (GFAP) and BMP2/4 in the spinal cord in days 1, 4, 7, 10 and 14. Next, normal rats received intrathecal exogenous BMP2/4 and the antagonist Noggin to assess the effect of BMP2/4 on astrocyte activation. In both experiments, von Frey filaments were used to evaluate changes in paw withdrawal threshold (PWT). In addition, Western blotting and immunofluorescence were performed to assess the expression of glial fibrillary acidic protein (GFAP), BMP2/4, p-Smad 1/5/8, p-STAT3 in the spinal cord. Firstly, SNL caused a significant increase in the expression of BMP4, while BMP2 levels remained unchanged. Secondly, exogenous BMP4 but not BMP2 induced a significant decrease in PWT, along with upregulation of GFAP. Moreover, exogenous BMP4 stimulated both p-Smad 1/5/8 and p-STAT3, while BMP2 only upregulated p-Smad 1/5/8. Finally, exogenous Noggin alleviated the decrease in PWT induced by BMP4, and reduced astrocyte activation, as well as p-STAT3 upregulation. Our results indicate only BMP4-and not BMP2-intervened in allodynia in rats by eliciting glial activation, probably through both p-Smad 1/5/8 andp-STAT3 signaling.
Learn More >Canine studies of spontaneous osteoarthritis (OA) pain add valuable data supporting drug treatment mechanisms that may translate to humans. A multicenter, randomized, double-blind, placebo- and active-controlled study was conducted in client-owned dogs with moderate OA pain to evaluate efficacy of LYA, an inhibitor of microsomal prostaglandin E synthase-1 (mPGES1), an EP4 antagonist (LYB), and carprofen, versus placebo. Of 255 dogs screened, 163 were randomized (placebo/LYA/LYB/carprofen: = 43/39/42/39) and 158 completed treatment. Efficacy versus placebo was assessed using Bayesian mixed-effect model for repeated measure analyses of the Canine Brief Pain Inventory (CBPI) pain interference score (PIS; primary endpoint), pain severity score, and overall impression, as well as the Liverpool Osteoarthritis in Dogs (LOAD) mobility score. The posterior probability that the difference to placebo was <0 at week 2 was 80% for LYA and 54% for LYB for CBPI PIS (both <95% predefined threshold). For secondary endpoints, the posterior probability that the difference to placebo was <0 at week 2 ranged from 89 to 96% for LYA and from 56 to 89% for LYB. The posterior probabilities comparing carprofen to placebo groups were ≥90% for all efficacy endpoints. The proportion of dogs with one or more adverse event was not significantly different from placebo (32.6%) for LYA (35.9%) or carprofen (25.6%), but the rate for LYB (59.5%) was higher versus placebo ( = 0.017). LYA treatment demonstrated consistent improvement in all efficacy measures, suggesting that inhibition of mPGES1 may be an effective treatment for chronic pain associated with OA.
Learn More >Pain assessment and treatment is challenging among persons with dementia (PWDs). To better understand reports of pain interference, we examined ratings made by PWDs, as well as corresponding ratings about PWDs, as reported by the caregiver. We aimed to assess alignment between and predictors of caregiver and PWD report of pain interference.
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