The journal of pain : official journal of the American Pain Society
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Various sensory and motor effects are associated with cancer treatment-induced peripheral neuropathy. The current method for capturing the multifaceted nature of neuropathy includes a combination of objective tests, clinician evaluation, and subjective patient report, an approach that is often not logistically feasible, especially for multisite trials. We report the performance of a brief yet comprehensive, easily administered measure, the Treatment-Induced Neuropathy Assessment Scale (TNAS), for assessing the severity and course of neuropathy across various cancer treatments. Data were derived from 4 longitudinal or cross-sectional patient cohorts (N = 573). Patients with multiple myeloma treated primarily with bortezomib and patients with colorectal cancer receiving oxaliplatin evaluated candidate items. Cognitive debriefing showed that all items were easy to understand, and this preliminary TNAS demonstrated reliability, validity, and sensitivity. Numbness/tingling was the most severe item, regardless of therapeutic agent. Although numbness and general pain were moderately correlated, patients perceived them as distinct. Most TNAS items were more severe at follow-up, demonstrating the sensitivity of the instrument to accumulating dose. The TNAS will be refined with further patient input, with final psychometric evaluation conducted in a new patient sample receiving treatments known to be associated with peripheral neuropathy. The nonpainful component of neuropathy may be more disabling than the pain component. ⋯ Our data suggest that the nonpainful components of neuropathy may be more disabling than the pain component during cancer treatment. Here we report data on sensory and motor symptoms reported by patients receiving neurotoxic cancer therapy, and we detail the development of a neuropathy assessment scale that follows regulatory guidance for patient-reported outcomes.
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Randomized Controlled Trial
Pharmacological modulation of the mitochondrial electron transport chain in paclitaxel-induced painful peripheral neuropathy.
Paclitaxel is an effective first-line chemotherapeutic with the major dose-limiting side effect of painful neuropathy. Mitochondrial dysfunction and oxidative stress have been implicated in paclitaxel-induced painful neuropathy. Here we show the effects of pharmacological modulation of mitochondrial sites that produce reactive oxygen species using systemic rotenone (complex I inhibitor) or antimycin A (complex III inhibitor) on the maintenance and development of paclitaxel-induced mechanical hypersensitivity in adult male Sprague Dawley rats. The maximally tolerated dose (5 mg/kg) of rotenone inhibited established paclitaxel-induced mechanical hypersensitivity. However, some of these inhibitory effects coincided with decreased motor coordination; 3 mg/kg rotenone also significantly attenuated established paclitaxel-induced mechanical hypersensitivity without any motor impairment. The maximally tolerated dose (.6 mg/kg) of antimycin A reversed established paclitaxel-induced mechanical hypersensitivity without any motor impairment. Seven daily doses of systemic rotenone or antimycin A were given either after paclitaxel administration or before and during paclitaxel administration. Rotenone had no significant effect on the development of paclitaxel-induced mechanical hypersensitivity. However, antimycin A significantly inhibited the development of paclitaxel-induced mechanical hypersensitivity when given before and during paclitaxel administration but had no effect when given after paclitaxel administration. These studies provide further evidence of paclitaxel-evoked mitochondrial dysfunction in vivo, suggesting that complex III activity is instrumental in paclitaxel-induced pain. ⋯ This study provides further in vivo evidence that mitochondrial dysfunction is a key contributor to the development and maintenance of chemotherapy-induced painful neuropathy. This work also indicates that selective modulation of the electron transport chain can induce antinociceptive effects in a preclinical model of paclitaxel-induced pain.
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This study sought to estimate (1) the prevalence of the co-occurrence of, (2) the association between, and (3) the sequence of onset of chronic pain and mental disorders in adolescents. We used weighted data (N = 6,483) from the National Comorbidity Survey Replication Adolescent Supplement (participants' age, 13-18 years). Lifetime chronic pain was assessed by adolescent self-report; lifetime DSM-IV mental disorders were assessed by the WHO Composite International Diagnostic Interview, complemented by parent report. Among the participants in the study, 1,600 of 6,476 (25.93%) had experienced any type of chronic pain and any mental disorder in their lifetime. All types of pain were related to mental disorders. The most substantial temporal associations were those with onset of mental disorders preceding onset of chronic pain, including those between affective disorders and headaches and any chronic pain; between anxiety disorders and chronic back/neck pain, headaches, and any chronic pain; between behavior disorders and headaches and any chronic pain; and between any mental disorder and chronic back/neck pain, headaches, and any chronic pain. ⋯ Findings indicate that affective, anxiety, and behavior disorders are early risk factors of chronic pain, thereby highlighting the relevance of child mental disorders for pain medicine. To improve prevention and interventions for chronic pain, integrative care should be considered.
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SCN9A is a key player in various rare monogenic pain disorders, including absence of pain or extreme pain, indicating that SCN9A is critical in human pain perception. This study aimed to investigate the association between the single-nucleotide polymorphisms (SNPs) in SCN9A and basal pain sensitivity variability in the general population. We used a combined tag and candidate SNP approach to explore possible associations between SCN9A SNPs and basal pain sensitivity in 309 healthy female Chinese undergraduates. Mechanical and heat pain sensitivity were measured, and a total of 28 SNPs were included in the final correlation analysis. Four candidate SNPs (rs6746030, rs7595255, rs12622743, and rs11898284) and 10 tag SNPs were associated (P < .05) with different pain perception phenotypes and exhibited opposite effects, resulting in either hypersensitivity or hyposensitivity. Furthermore, of all these SNPs, rs16851778 showed the strongest significant (P = .003) association with lower mechanical pain sensitivity, which was strengthened in a subsequent replication sample with 260 young patients scheduled for elective gynecological surgery. These findings provided evidence that the variability of basal pain sensitivity was associated with SCN9A polymorphisms in the general population. ⋯ This study demonstrated that several candidate and tag SCN9A SNPs were associated with hypersensitivity or hyposensitivity to basal experimental pain stimulation. Moreover, we identified a novel SNP, i,e,, rs16851778, that was associated with lower mechanical pain sensitivity and that was strengthened in a subsequent replication sample.
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Posttraumatic stress disorder (PTSD) and chronic pain often co-occur and exacerbate each other. Elucidating the mechanism of this co-occurrence therefore has clinical importance. Previously, patients with PTSD with chronic pain were found to demonstrate a unique paradoxical pain profile: hyperresponsiveness together with hyposensitivity to pain. Our aim was to examine whether 2 seemingly paradoxical facets of PTSD (anxiety and dissociation) underlie this paradoxical profile. Patients with PTSD (n = 32) and healthy control individuals (n = 43) underwent psychophysical testing and completed questionnaires. Patients with PTSD had higher pain thresholds and higher pain ratings to suprathreshold stimuli than control individuals. Pain thresholds were positively associated with dissociation levels and negatively associated with anxiety sensitivity levels. Experimental pain ratings were positively associated with anxiety sensitivity and negatively related to dissociation levels. Chronic pain intensity was associated with anxiety, anxiety sensitivity, and pain catastrophizing. It appears that reduced conscious attention toward incoming stimuli, resulting from dissociation, causes delayed response in pain threshold measurement, whereas biases toward threatening stimuli and decreased inhibition, possibly caused by increased anxiety, are responsible for the intensification of experimental and chronic pain. The paradoxical facets of PTSD and their particular influences over pain perception seem to reinforce the coexistence of PTSD and chronic pain, and should be considered when treating traumatized individuals. ⋯ This article provides new information regarding the underlying mechanism of the coexistence of PTSD and chronic pain. This knowledge could help to provide better management of PTSD and chronic pain among individuals in the aftermath of trauma.