The journal of pain : official journal of the American Pain Society
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Chronic pain is common during adolescence and young adulthood and is associated with poor quality of life, depression, and functional disability. Recognizing that chronic pain has significant consequences, it is important to identify modifiable health behaviors that may place young adults at risk for chronic pain. This study examines associations between chronic musculoskeletal pain and smoking in young adult twins (n = 1,588, ages 18-30) participating in a statewide twin registry. Twins completed questionnaires assessing smoking, mood (anxiety, depressive symptoms, and stress), and chronic musculoskeletal pain. Analyses examined associations between chronic pain and smoking, particularly the role of genetics/shared familial factors and psychological symptoms. As predicted, results revealed a near-2-fold increased risk for chronic musculoskeletal pain in twins who currently smoked compared to nonsmokers, even when accounting for psychological factors. Results of within-pair analyses were only minimally attenuated, suggesting that associations between smoking and chronic musculoskeletal pain are better accounted for by nonshared factors than by shared familial factors/genetic effects. Future twin research is needed to identify what nonshared factors (eg, attitudes, direct effects of smoking on pain) contribute to these associations to further understand comorbidity. Longitudinal studies and recruitment of participants prior to smoking initiation and chronic pain onset will better identify causal associations. ⋯ This article describes associations between musculoskeletal pain and smoking in young adult twins, taking into account psychological symptoms. Findings highlight the importance of nonshared factors in associations between pain and smoking and the need to explore the roles of lifestyle, individual attitudes, and direct effects of smoking on pain.
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A common variant in the mu-opioid receptor gene (OPRM1) has been associated with response to opioid analgesia. Our previous data revealed significantly higher amounts of morphine self-administered by patients carrying the 118G allele compared to those with the 118A allele after elective cesarean section. In this study, the association of this genetic variation with pressure pain, postoperative pain scores, and amount of morphine used was investigated in 973 patients undergoing scheduled total hysterectomy under general anesthesia. Preoperative pressure pain threshold and tolerance were also measured for most patients. For pressure pain, OPRM1 genotype was not significantly associated with either pain threshold or pain tolerance. Statistically significant associations were found for postoperative pain and the total amount of morphine used, with the GG group reporting higher pain scores and using the most morphine. When analysis was stratified by ethnic group, differences in weight-adjusted morphine for the 3 genotypic groups were also significant for the Chinese and Asian Indians. These results extend our previous finding on the association of higher self-reported pain and morphine use for acute postoperative pain with OPRM1 118G to patients who had total hysterectomy under general anesthesia. ⋯ In a large cohort of patients undergoing hysterectomy, we found large variability in the self-rated pain scores and the amount of morphine required for pain relief. Both are associated with OPRM1 genotypes and preoperative experimental pressure pain threshold. Experimental pressure pain tolerance is also associated with postoperative pain.
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The default mode network (DMN), a group of brain regions implicated in passive thought processes, has been proposed as a potentially informative neural marker to aid in novel treatment development. However, the DMN's internal connectivity and its temporal relationship (ie, functional network connectivity) with pain-related neural networks in chronic pain conditions is poorly understood, as is the DMN's sensitivity to analgesic effects. The current study assessed how DMN functional connectivity and its temporal association with 3 pain-related networks changed after rectal lidocaine treatment in irritable bowel syndrome patients. Eleven females with irritable bowel syndrome underwent a rectal balloon distension paradigm during functional magnetic resonance imaging in 2 conditions: natural history (ie, baseline) and lidocaine. Results showed increased DMN connectivity with pain-related regions during natural history and increased within-network connectivity of DMN structures under lidocaine. Further, there was a significantly greater lag time between 2 of the pain networks, those involved in cognitive and in affective pain processes, comparing lidocaine to natural history. These findings suggest that 1) DMN plasticity is sensitive to analgesic effects, and 2) reduced pain ratings via analgesia reflect DMN connectivity more similar to pain-free individuals. Findings show potential implications of this network as an approach for understanding clinical pain management techniques. ⋯ This study shows that lidocaine, a peripheral analgesic, significantly altered DMN connectivity and affected its relationship with pain-related networks. These findings suggest that the DMN, which is hypothesized to represent non-goal-oriented activity, is sensitive to analgesic effects and could be useful to understand pain treatment mechanisms.
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The use of paclitaxel (Taxol), a microtubule stabilizer, for cancer treatment is often limited by its associated peripheral neuropathy (chemotherapy-induced peripheral neuropathy [CIPN]), which predominantly results in sensory dysfunction, including chronic pain. Here we show that paclitaxel CIPN was associated with induction of chemokine monocyte chemoattractant protein-1 (MCP-1) and its cognate receptor CCR2 in primary sensory neurons of dorsal root ganglia. Immunostaining revealed that MCP-1 was mainly expressed in small nociceptive neurons whereas CCR2 was expressed in large and medium-sized myelinated neurons. Direct application of MCP-1 consistently induced intracellular calcium increases in dorsal root ganglia large and medium-sized neurons but not in small neurons mainly dissociated from paclitaxel-treated but not vehicle-treated animals. Paclitaxel also induced increased expression of MCP-1 in spinal astrocytes, but no CCR2 signal was detected in the spinal cord. Local blockade of MCP-1/CCR2 signaling by anti-MCP-1 antibody or CCR2 antisense oligodeoxynucleotides significantly attenuated paclitaxel CIPN phenotypes including mechanical hypersensitivity and loss of intraepidermal nerve fibers in hindpaw glabrous skin. These results suggest that activation of paracrine MCP-1/CCR2 signaling between dorsal root ganglion neurons plays a critical role in the development of paclitaxel CIPN, and targeting MCP-1/CCR2 signaling could be a novel therapeutic approach. ⋯ CIPN is a severe side effect accompanying paclitaxel chemotherapy and lacks effective treatments. The current study suggests that blocking MCP-1/CCR2 signaling could be a new therapeutic strategy to prevent or reverse paclitaxel CIPN. This preclinical evidence encourages future clinical evaluation of this strategy.