Articles: opioid.
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Anesthesia and analgesia · Apr 2023
Role of Tumor Necrosis Factor Receptor 1-Reactive Oxygen Species-Caspase 11 Pathway in Neuropathic Pain Mediated by HIV gp120 With Morphine in Rats.
Recent clinical research suggests that repeated use of opioid pain medications can increase neuropathic pain in people living with human immunodeficiency virus (HIV; PLWH). Therefore, it is significant to elucidate the exact mechanisms of HIV-related chronic pain. HIV infection and chronic morphine induce proinflammatory factors, such as tumor necrosis factor (TNF)α acting through tumor necrosis factor receptor I (TNFRI). HIV coat proteins and/or chronic morphine increase mitochondrial superoxide in the spinal cord dorsal horn (SCDH). Recently, emerging cytoplasmic caspase-11 is defined as a noncanonical inflammasome and can be activated by reactive oxygen species (ROS). Here, we tested our hypothesis that HIV coat glycoprotein gp120 with chronic morphine activates a TNFRI-mtROS-caspase-11 pathway in rats, which increases neuroinflammation and neuropathic pain. ⋯ These results suggest that spinal TNFRI-mtROS-caspase 11 signal pathway plays a critical role in the HIV-associated neuropathic pain state, providing a novel approach to treating chronic pain in PLWH with opioids.
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Delphi study to explore a new diagnosis for "ineffective" long-term opioid therapy for chronic pain.
A challenge in clinical, research, and policy spheres is determining whether and how to apply the Diagnostic and Statistical Manual-5 Opioid Use Disorder criteria to patients receiving long-term opioid therapy (LTOT) for the management of chronic pain. This study explored perspectives on the merits of creating a new diagnostic entity to characterize the problems that arise for certain patients prescribed LTOT and develop consensus on its definition and diagnostic criteria. We conducted 3 rounds of online surveys and held one discussion-based workshop to explore a new diagnostic entity and generate consensus with subject matter experts (n = 51) in pain and opioid use disorder, including a wide range of professional disciplines. ⋯ A subgroup of expert panelists further refined the new diagnostic entity definition and criteria. Consensus on potential criteria for the new diagnostic entity was reached and further refined by a subgroup of experts. This Delphi study represents the opinions of a small group of subject matter experts; perspectives from other experts and additional stakeholder groups (including patients) are warranted.
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Painful diabetic peripheral neuropathy (PDPN) is one of the major complications of diabetes. Currently, centrally acting drugs and topical analgesics are used for treating PDPN. These drugs have adverse effects; some are ineffective, and treatment with opioids is associated with use dependence and addiction. ⋯ Application of RTX cream to the hind limbs suppresses thermal hyperalgesia in streptozotocin-induced diabetic rats and mini pigs without any adverse effects as compared with capsaicin at therapeutic doses, which induces intense pain during application. Resiniferatoxin cream also decreases the expression of TRPV1 in the peripheral nerve endings and suppresses TRPV1-mediated calcitonin gene-related peptide release in the skin samples of diabetic rats and mini pigs. Our preclinical data confirm that RTX topical formulation is an effective treatment option for PDPN.
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Cannabis has been used since ancient times for medical and recreational research. This review article will document the validity of how medical cannabis can be utilized for chronic nonmalignant pain management. ⋯ Current cannabis research has shown that medical cannabis is indicated for symptom management for many conditions not limited to cancer, chronic pain, headaches, migraines, and psychological disorders (anxiety and post-traumatic stress disorder). Δ9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are active ingredients in cannabis that modulate a patient's symptoms. These compounds work to decrease nociception and symptom frequency via the endocannabinoid system. Research regarding pain management is limited within the USA as the Drug Enforcement Agency (DEA) classifies it as a schedule one drug. Few studies have found a limited relationship between chronic pain and medical cannabis use. A total of 77 articles were selected after a thorough screening process using PubMed and Google Scholar. This paper demonstrates that medical cannabis use provides adequate pain management. Patients suffering from chronic nonmalignant pain may benefit from medical cannabis due to its convenience and efficacy.
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Editorial Comment
Opioids and autism spectrum disorder: liaisons dangereuses?
A recent laboratory study in the Journal examined the effects of repeated exposures of neonatal mice to fentanyl on autism-like behaviour via opioid receptor-mediated DNA hypermethylation of the Grin2B gene, which encodes the GluN2B subunit of the NMDA receptor. These experiments provide mechanisms and biological plausibility but do not directly demonstrate that opioid exposure in early life induces autism spectrum disorder in humans. Experimental modelling of human neuropsychiatric disorders is extremely challenging since most subjective psychiatric symptoms used to establish diagnosis in humans cannot be convincingly ascertained in laboratory rodents. While some human epidemiological data show associations between repeated exposures to opioids during early life, it remains undetermined whether opioid exposure is an independent risk factor for developing autism spectrum disorder in the young.