Mol Pain
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Telomere length, a measure of cellular aging, is inversely associated with chronic pain severity. While psychological resilience factors (e.g., optimism, acceptance, positive affect, and active coping) are associated with lower levels of clinical pain and greater physical functioning, it is unknown whether resilience may buffer against telomere shortening in individuals with chronic pain. Additionally, a broader conceptualization of resilience that includes social and biobehavioral factors may improve our understanding of the relationship between resilience, chronic pain, and health outcomes. ⋯ In regression analyses controlling for sex, race, age, and characteristic pain intensity, greater psychological resilience and psychosocial/biobehavioral resilience were associated with longer telomeres ( p = .0295 and p = .0116, respectively). When compared, psychosocial/biobehavioral resilience was significantly more predictive of telomere length than psychological resilience ( p < .0001). Findings are promising and encourage further investigations to enhance understanding of the biological interface of psychosocial and biobehavioral resilience factors in individuals with musculoskeletal chronic pain conditions.
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The catechol-O-methyltransferase Val158Met polymorphism has been associated with alterations in pain perception, but the influence of the polymorphism on pain perception in patients with chronic pain receiving daily opioid therapy has not been previously reported. The primary aim of this study was to investigate the effects of the catechol-O-methyltransferase Val158Met polymorphism on heat pain perception in a cohort of adults receiving daily opioid therapy for chronic pain. Adults with chronic pain consecutively admitted to an outpatient pain rehabilitation program who met inclusion criteria and were receiving daily opioid therapy were recruited for study participation (N = 142). ⋯ No significant association was observed between heat pain perception and genotype under the additive model of allele effects. Among patients with chronic pain who were receiving daily opioids, the Val/Met genotype was associated with hyperalgesia using a measure of heat pain perception that has been previously indicative of opioid-induced hyperalgesia in other heterogeneous samples of adults with chronic pain. This study contributes to the emerging understanding of how catechol-O-methyltransferase activity affects pain perception in the context of daily opioid use, and these findings may be useful in the design of future trials aimed at investigating the potential efficacy of ß-2 adrenergic receptor antagonism for opioid-induced hyperalgesia.
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Radiotherapy-related pain is a common adverse reaction with a high incidence among cancer patients undergoing radiotherapy and remarkably reduces the quality of life. However, the mechanisms of ionizing radiation-induced pain are largely unknown. In this study, mice were treated with 20 Gy X-ray to establish ionizing radiation-induced pain model. ⋯ Additionally, the phosphorylated extracellular regulated protein kinases (ERK) and Jun NH2-terminal Kinase (JNK) in pain neural pathway were induced by X-ray treatment. Our findings indicated that activation of transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 is essential for the development of X-ray-induced allodynia. Furthermore, our findings suggest that targeting on transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1 may be promising prevention strategies for X-ray-induced allodynia in clinical practice.
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Descending nociceptive modulation from the supraspinal structures has an important role in cancer-induced bone pain (CIBP). Midbrain ventrolateral periaqueductal gray (vlPAG) is a critical component of descending nociceptive circuits; nevertheless, its precise cellular and molecular mechanisms involved in descending facilitation remain elusive. Our previous study has shown that the activation of p38 MAPK in vlPAG microglia is essential for the neuropathic pain sensitization. ⋯ Moreover, the intrathecal administration of JNK inhibitors SP600125 reduced the expression of glial fibrillary acidic protein, while microinjection of the SP600125 decreased the mechanical allodynia of CIBP rats. These results suggested that CIBP is associated with astrocyte activation in the vlPAG that probably participates in driving descending pain facilitation through the JNK MAPK signaling pathway. To sum up, these findings reveal a novel site of astrocytes modulation of CIBP.
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Neuropeptide Y signaling plays an important role in inhibiting chronic pain in the spinal cord of mice. However, little is known about the respective roles of two major neuropeptide Y receptors, Y1R and Y2R, in evoked and spontaneous pain behavior under normal physiological condition. Using intrathecal administration approach, we found that pharmacological inhibition of Y2R, unexpectedly, gave rise to spontaneous pain behavior. ⋯ Remarkably, the activation of Y1R produced powerful analgesic effect: blocking both evoked and spontaneous pain behavior resulted from Y2R antagonism. These findings highlight the pivotal role of endogenous Y2R in gating mechanical and spontaneous pain transmission. Importantly, our results suggest that Y1R could be a therapeutic target that may be exploited for alleviating spontaneous pain without affecting acute pain transmission.