Articles: neuropathic-pain.
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Understanding molecular alterations associated with peripheral inflammation is a critical factor in selectively controlling acute and persistent pain. The present report employs in situ hybridization of the 2 opioid precursor mRNAs coupled with quantitative measurements of 2 peptides derived from the prodynorphin and proenkephalin precursor proteins: dynorphin A 1-8 and [Met5]-enkephalin-Arg6-Gly7-Leu8. In dorsal spinal cord ipsilateral to the inflammation, dynorphin A 1-8 was elevated after inflammation, and persisted as long as the inflammation was sustained. ⋯ These data support the idea that activation of endogenous opioids, notably dynorphin, is a dynamic indicator of persistent pain states in spinal cord and of nerve injury in DRG. PERSPECTIVE: This is a systematic, quantitative assessment of dynorphin and enkephalin peptides and mRNA in dorsal spinal cord and DRG neurons in response to peripheral inflammation and axotomy. These studies form the foundational framework for understanding how endogenous spinal opioid peptides are involved in nociceptive circuit modulation.
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Prevention of phantom limb pain is one of the biggest and still largely unsolved challenges in perioperative medicine. Despite many study efforts and optimization of postoperative pain treatment over the last 30 years, a significant reduction in the incidence of phantom limb pain has not been achieved. ⋯ In addition to regional anesthesia, NMDA antagonists, gabapentinoids, antidepressants and systemic lidocaine could play a relevant role. The aim of this pharmacological intervention was the modification of the pathophysiological changes in peripheral nerves and in the central nervous system after amputation.
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Neuropathic pain (NP) remains a major debilitating condition affecting more than 26% of breast cancer survivors worldwide. NP is diagnosed using a validated 10-items Douleur Neuropathique - 4 screening questionnaire which is administered 3 months after surgery and requires patient-doctor interaction. To develop an effective prognosis model admissible soon after surgery, without the need for patient-doctor interaction, we sought to [1] identify specific pain characteristics that can help determine which patients may be susceptible to NP after BC surgery, and 2) assess the utility of machine learning models developed in objective [1] as a knowledge discovery tool for downstream analysis. ⋯ Modern machine learning models show improvements over traditional least square regression in predicting of DN4-interview score. Penalized regression methods and the Gradient boosting model out-perform other models. As a predictor discovery tool, machine learning algorithms identify relevant predictors for DN4-interview score that remain statistically significant indicators of neuropathic pain in the classification model. Anxiety, type of surgery and acute pain on movement remain the most useful predictors for neuropathic pain.
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Fifth lumbar (L5) nerve injury in rats causes neuropathic pain manifested with thermal and mechanical hypersensitivity in the ipsilateral hind paw. This study aimed to determine whether the elimination of unmyelinated primary afferents of the adjacent uninjured nerves (L3 and L4) would alleviate peripheral neuropathic pain. Different concentrations of capsaicin or its analog, resiniferatoxin (RTX), were applied perineurally on either the left L4 or L3 and L4 nerves in Wistar rats whose left L5 nerves were ligated and cut. ⋯ RTX application did not cause degenerative or ultrastructural changes in the treated nerves and corresponding DRGs. The results demonstrate that RTX induces neuroplasticity, rather than structural changes in primary afferents, that are responsible for alleviating hypersensitivity and chronic pain. Furthermore, this study suggests that treating uninjured adjacent spinal nerves may be used to manage chronic neuropathic pain following peripheral nerve injury.