Articles: neuropathic-pain.
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Dorsal root ganglion stimulation (DRGS) is an established method for treating persistent and severe pain conditions. However, performing DRGS has significant challenges. Current DRGS systems are expensive, hindering accessibility for many patients and health care systems. Additionally, placing DRGS devices requires specialized training in epidural techniques and lead anchoring methods. Technical and financial requirements also limit the clinical applicability and availability of DRGS. ⋯ To our knowledge, this feasibility cadaver study is the first of its kind to examine the accuracy and efficiency of a fluoroscopy-guided transforaminal approach to place injectable electrodes near the DRG. These promising results suggest that this method could be a viable alternative to existing DRGS techniques, warranting further investigation into its clinical potential.
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Nerve injury-induced changes in gene expression in the dorsal root ganglion (DRG) contribute to the genesis of neuropathic pain. SYNCRIP, an RNA-binding protein, is critical for the stabilisation of gene expression. Whether SYNCRIP participates in nerve injury-induced alterations in DRG gene expression and nociceptive hypersensitivity is unknown. ⋯ SYNCRIP contributes to the induction and maintenance of neuropathic pain likely through stabilising expression of CCR2 in injured DRG. SYNCRIP may be a potential target for treating this disorder.
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Anesthesia and analgesia · Nov 2024
Involvement of Spinal Neuroplastin 65 in Neuropathic Pain by GABAA Receptor α2 Subunit Regulation.
Neuropathic pain (NP) is a highly challenging condition with complex pathological mechanisms, and the spinal gamma aminobutyric acid A receptor receptor plays a crucial role in its progression. Recent studies have revealed a potential interaction between neuroplastin 65 (NP65) and gamma aminobutyric acid A receptor α2 subunit (GABAAR-α2) on the cell surface. We hypothesize that NP65 is involved in the pathogenesis of NP by regulating the level of GABAAR-α2. ⋯ NP65 modulates the level of GABAAR-α2 through the CaN-NFATc4 signaling pathway, which may serve as the underlying mechanism of NP.
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Microglia take on an altered morphology during chronic opioid treatment. This morphological change is broadly used to identify the activated microglial state associated with opioid side effects, including tolerance and opioid-induced hyperalgesia (OIH). Microglia display similar morphological responses in the spinal cord after peripheral nerve injury (PNI). ⋯ After PNI, we identify an early proliferative transcriptional event across models that precedes the upregulation of histological markers of microglial activation. However, we found no proliferative transcriptional response associated with opioid-induced microglial activation, consistent with histological data, indicating that the number of microglia remains stable during morphine treatment, whereas their morphological response differs from PNI models. Collectively, these results establish the diversity of pain-associated microglial transcriptomic responses and point towards the targeting of distinct insult-specific microglial responses to treat OIH, PNI, or other central nervous system pathologies.
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Randomized Controlled Trial
Topically applied novel TRPV1 receptor antagonist, ACD440 Gel, reduces evoked pain in healthy volunteers, a randomized, double-blind, placebo-controlled, crossover study.
The TRPV1 receptor is a key molecule in pain generation. Previous development of oral TRPV1-antagonists was halted due to systemic heat insensitivity and body temperature alterations. The present Phase 1b study investigated the efficacy, safety and plasma exposure of a topically administered TRPV1-antagonist (ACD440 Gel) in healthy subjects. ⋯ This study demonstrates that the topical administration of a TRPV1-antagonist, ACD440 Gel, has potential as a new treatment for painful conditions affecting the skin, such as chronic peripheral neuropathic pain, without any local or systemic side effects.