Pain
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Peripheral nerve regeneration is associated with pain in several preclinical models of neuropathic pain. Some neuropathic pain conditions and preclinical neuropathic pain behaviors are improved by sympathetic blockade. In this study, we examined the effect of a localized "microsympathectomy," ie, cutting the gray rami containing sympathetic postganglionic axons where they enter the L4 and L5 spinal nerves, which is more analogous to clinically used sympathetic blockade compared with chemical or surgical sympathectomy. ⋯ Microsympathectomy reduced functional regeneration as measured by myelinated action potential propagation through the injury site and denervation-induced atrophy of the tibial-innervated gastrocnemius muscle at day 10. Microsympathectomy plus CCL2 knockdown had behavioral effects similar to microsympathectomy alone. The results show that local sympathetic effects on neuropathic pain may be mediated in a large part by the effects on expression of CCL2, which in turn regulates the regeneration process.
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Despite tremendous efforts to increase the reliability of pain measures and other self-report instruments, improving or even evaluating the reliability of change scores has been largely neglected. In this study, we investigate the ability of 2 instruments from the Patient-Reported Outcomes Measurement Information System, pain interference (6 items) and pain behavior (7 items), to reliably detect individual changes in pain during the postsurgical period of a hernia repair in 98 patients who answered daily diaries over almost 3 weeks after surgery. ⋯ We found (1) that near perfect reliability can be achieved if measures from all days over the whole study period, obtained with all pain interference or pain behavior items, were used to estimate the observed change, (2) that various combinations of the number of items and the number of measurement occasions could achieve acceptable reliability, and (3) that computer adaptive testings were superior to short forms in achieving sufficient reliability. We conclude that the specific strategy for assessing individual postoperative change in pain experience must be selected carefully.
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Clinically significant new or worsening pain (CSNWP) is a common, yet often overlooked, sequelae of sexual assault. Little is known regarding factors influencing the development of CSNWP in sexual assault survivors. The current study used data from a recently completed prospective study to evaluate whether posttraumatic alterations in arousal and reactivity in the early aftermath of sexual assault influence the transition from acute to clinically significant new or worsening persistent pain. ⋯ A structural equation model adjusted for age, race, past trauma exposure, and preassault pain levels suggested that posttraumatic alterations in arousal/reactivity symptoms 1 week after assault partially mediated the transition from acute to persistent CSNWP. A significant portion (41%) of women sexual assault survivors develop CSNWP 6 weeks postassault. Posttraumatic arousal/reactivity symptoms in the early aftermath of assault contribute to CSNWP development; such symptoms are potential targets for secondary preventive interventions to reduce chronic postassault pain.
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Excess pain after visceral provocation has been suggested as a marker for chronic pelvic pain risk in women. However, few noninvasive tests have been validated that could be performed readily on youth in early risk windows. Therefore, we evaluated the validity and reliability of a noninvasive bladder pain test in 124 healthy premenarchal females (median age 11, [interquartile range 11-12]), as previously studied in adult women. ⋯ We found strong retest reliability for bladder pain at standard levels of sensory urgency in 21 adolescents who attended repeat visits at 6 to 12 months (intraclass correlations = 0.88-0.90). Noninvasive bladder pain testing seems reproducible in adolescent females and may predict abdominal pain symptomatology. Confirmation of our findings and further investigation of the bladder test across menarche will help establish how visceral sensitivity contributes to the early trajectory of pelvic pain risk.
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A modern approach for cancer treatment is the use of immunotherapy, and particularly immune checkpoint inhibitors, such as anti-programmed cell death protein 1 (PD-1), alone and in combination with chemotherapy. The PD-1 pathway plays a crucial role in inhibiting immune responses and recently has been shown to modulate neuronal activity. However, the impact of PD-1 blockade on the development of chemotherapy-induced peripheral neuropathy is currently unknown. ⋯ Mice treated with paclitaxel or cotherapy had increased macrophage presence in the DRG, and all treated groups presented an altered expression of microglia markers in the dorsal horn of the spinal cord. We conclude that combining anti-PD-1 immunotherapy with paclitaxel does not increase the severity of paclitaxel-induced peripheral neuropathy. However, because anti-PD-1 treatment caused significant changes in DRG and spinal cord immunity, caution is warranted when considering immune checkpoint inhibitors therapy in patients with a high risk of developing neuropathy.