Pain
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Chronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered by pain, provide insight into biological treatment targets, and help identify at-risk patients who might benefit from early intervention. ⋯ Acute to Chronic Pain Signatures will provide the most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken to date. Data and analytic resources generatedby A2CPS will be shared with the scientific community in hopes that other investigators will extract valuable insights beyond A2CPS's initial findings. This article will review the identified biomarkers and rationale for including them, the current state of the science on biomarkers of the transition from acute to chronic pain, gaps in the literature, and how A2CPS will address these gaps.
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Chronic pain (CP) is often accompanied by mental disorders (MDs). However, little is known concerning the long-term effect of MDs, personality traits, and early-life traumatic events (ETEs) on CP course. Accordingly, we aimed to prospectively assess the associations of major depressive disorders (MDDs), anxiety disorders, personality traits, and ETEs with the incidence and the persistence of CP in middle-aged and older community dwellers. ⋯ Our results suggest that personality traits are associated with both CP occurrence and persistence, whereas the MDDs may be more associated with CP persistence. Both personality and MDD are accessible to psychotherapy, and MDD is also accessible to pharmacotherapy. Hence, these therapeutic measures might decrease the risk of CP and its persistence.
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Although preclinical studies generally report robust antinociceptive effects of cannabinoids in rodent persistent pain models, randomized controlled trials in chronic pain patients report limited pain relief from cannabis/cannabinoids. Differences between animal and human studies that may contribute to these discrepant findings include route of cannabis/cannabinoid administration, type of cannabis/cannabinoid, and how pain is measured. To address these factors, rats with complete Freund adjuvant (CFA)-induced hind paw inflammation were exposed acutely or repeatedly to vaporized cannabis extract that was either tetrahydrocannabinol (THC) or cannabidiol (CBD)dominant. ⋯ Acute exposure to vaporized CBD-dominant cannabis extract (200 mg/mL) did not produce any effects in either sex; repeated exposure to this extract (100, 200, or 400 mg/mL) decreased mechanical allodynia in male rats only. Sex differences (or lack thereof) in the effects of vaporized cannabis extracts were not explained by sex differences in plasma levels of THC, CBD, or their major metabolites. These results suggest that although vaporized THC-dominant extract is likely to be modestly effective against inflammatory pain in both male and female rats, tolerance may develop, and the CBD-dominant extract may be effective only in male rats.
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In the United States, cannabis is increasingly used to manage chronic pain. Veterans Health Administration (VHA) patients are disproportionately affected by pain and may use cannabis for symptom management. Because cannabis use increases the risk of cannabis use disorders (CUDs), we examined time trends in CUD among VHA patients with and without chronic pain, and whether these trends differed by age. ⋯ From 2016 to 2019, CUD prevalence among patients age ≥65 with chronic pain increased significantly more (0.63%-1.01%) than those without chronic pain (0.28%-0.47%) and was highest among those with ≥2 pain conditions. Over time, CUD prevalence has increased more among VHA patients with chronic pain than other VHA patients, with the highest increase among those age ≥65. Clinicians should monitor symptoms of CUD among VHA patients and others with chronic pain who use cannabis, and consider noncannabis therapies, particularly because the effectiveness of cannabis for chronic pain management remains inconclusive.
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Chemotherapy-induced peripheral neuropathic pain (CIPNP) is an adverse effect observed in up to 80% of patients of cancer on treatment with cytostatic drugs including paclitaxel and oxaliplatin. Chemotherapy-induced peripheral neuropathic pain can be so severe that it limits dose and choice of chemotherapy and has significant negative consequences on the quality of life of survivors. Current treatment options for CIPNP are limited and unsatisfactory. ⋯ In addition, the levels of protein ERK, a marker for neuronal activity, were significantly reduced in dorsal root ganglion neurons derived from TRPM3 deficient mice compared with control after oxaliplatin administration. Moreover, intraperitoneal injection of a TRPM3 antagonist, isosakuranetin, effectively reduced the oxaliplatin-induced pain behavior in response to cold and mechanical stimulation in mice with an acute form of oxaliplatin-induced peripheral neuropathy. In summary, TRPM3 represents a potential new target for the treatment of neuropathic pain in patients undergoing chemotherapy.