The journal of pain : official journal of the American Pain Society
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The rationale of spinal administration of endothelin-1(ET-1) mediated anti-nociceptive effect has not been elucidated. ET-1 is reported to promote nuclear effluxion of histone deacetylase 5 (HDAC5) in myocytes, and spinal HDAC5 is implicated in modulation of pain processing. In this study, we aimed to investigate whether central ET-1 plays an anti-nociceptive role by facilitating spinal HDAC5 nuclear shuttling under neuropathic pain. ⋯ Therefore, inducing spinal GABAergic neuronal HDAC5 nuclear exportation may be a novel therapeutic approach for managing neuropathic pain. PERSPECTIVE: Neuropathic pain is intractable in a clinical setting, and epigenetic regulation is considered to contribute to this processing. Characterizing the anti-nociceptive effect of ET-1 and investigating the associated epigenetic mechanisms in animal models may lead to the development of new therapeutic strategies and targets for treating neuropathic pain.
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Chronic pain is a significant comorbid condition among individuals with opioid use disorder (OUD). However, due to conflicting perceptions of responsibility, structural barriers, and a lack of widely applied standards of care, it is unclear what the landscape of chronic pain management looks like in addiction medicine. Using a national opioid surveillance system, we analyzed survey data from new entrants (n = 14,449) to 225 OUD treatment centers from 2013 to 2018, as well as an online survey among a subset of respondents (n = 309). ⋯ In order to improve poor outcomes among OUD patients, interdisciplinary collaboration/care, along with evidence-based policies or processes for quality pain management in addiction care need to be prioritized. PERSPECTIVE: This article suggests chronic pain is commonly reported, yet not managed by many OUD treatment programs, increasing the likelihood of opioid relapse. In order to improve low retention and success rates among OUD patients, interdisciplinary collaboration, evidence-based policies or processes (eg, referral) for quality pain management in addiction care need to be prioritized.
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Observational Study
Analgesic Effects of Topical Amitriptyline in Patients with Chemotherapy-Induced Peripheral Neuropathy: Mechanistic Insights from Studies in Mice.
Oral amitriptyline hydrochloride (amitriptyline) is ineffective against some forms of chronic pain and is often associated with dose-limiting adverse events. We evaluated the potential effectiveness of high-dose topical amitriptyline in a preliminary case series of chemotherapy-induced peripheral neuropathy patients and investigated whether local or systemic adverse events associated with the use of amitriptyline were present in these patients. We also investigated the mechanism of action of topically administered amitriptyline in mice. ⋯ This analgesic action appeared to be mediated through local inhibition of voltage-gated sodium channels. PERSPECTIVE: Our preliminary case series suggested that topical amitriptyline could provide effective pain relief for chemotherapy-induced peripheral neuropathy patients without any systemic or local adverse events. Investigation of the mechanism of this analgesic action in mice revealed that this activity was mediated through local inhibition of nociceptor Nav channels.