Background: Resiniferatoxin (RTX) is a potent analog of capsaicin and activates transient receptor potential (TRP) vanilloid type (TRPV) 1. In the current study, we investigated the preventive effect of perineural RTX on the development of cold hypersensitivity induced by spinal nerve ligation (SNL) in rats. Furthermore, we examined the association between the expression level of TRPV1, TRP ankyrin type (TRPA) 1 and TRP melastatin type (TRPM) 8 in the dorsal root ganglion (DRG) and cold hypersensitivity after SNL.
Results: RTX pretreatment prevented the development of SNL-induced hypersensitivity to mechanical, thermal, and cold stimuli. Western blot analysis 4 weeks after RTX pretreatment showed that RTX pretreatment decreased the protein expression level of SNL-induced TRPM8, but not TRPV1 or TRPA1, in the DRG of SNL rats. Immunofluorescent analysis revealed that up-regulated TRPM8-stained neurons after SNL co-localized with neurofilament 200-positive neurons located in the DRG.
Conclusions: Pretreatment with perineural RTX significantly inhibits SNL-induced mechanical, thermal, and cold hypersensitivity. The antinociceptive effect of perineural RTX, especially on cold hypersensitivity, may be related to the suppression of TRPM8 expression in DRG.
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http://dx.doi.org/10.1186/s12868-016-0273-8 | DOI Listing |
Pain
November 2024
Center for Neuroscience, Indian Institute of Science, Bengaluru, Karnataka, India.
The neural mechanisms of the affective-motivational symptoms of chronic pain are poorly understood. In chronic pain, our innate coping mechanisms fail to provide relief. Hence, these behaviors are manifested at higher frequencies.
View Article and Find Full Text PDFFront Pharmacol
December 2024
Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile.
Cold allodynia is a debilitating symptom of orofacial neuropathic pain resulting from trigeminal nerve damage. The molecular and neural bases of this sensory alteration are still poorly understood. Here, using chronic constriction injury (CCI) of the infraorbital nerve (IoN) (IoN-CCI) in mice, combined with behavioral analysis, Ca imaging and patch-clamp recordings of retrogradely labeled IoN neurons in culture, immunohistochemistry, and adeno-associated viral (AAV) vector-based delivery , we explored the mechanisms underlying the altered orofacial cold sensitivity resulting from axonal damage in this trigeminal branch.
View Article and Find Full Text PDFCells
November 2024
Department of Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Post-traumatic trigeminal neuropathy (PTTN) is a sensory abnormality caused by injury to the trigeminal nerve during orofacial surgery. However, existing analgesics are ineffective against PTTN. Abnormal microglial activation in the caudal part of the spinal trigeminal nucleus caudal part (Sp5C), where the central trigeminal nerve terminals reside, plays an important role in PTTN pathogenesis.
View Article and Find Full Text PDFJ Pain
December 2024
Pharmacology and Therapeutics, School of Medicine, Human Biology Building, University of Galway, Galway, Ireland; Galway Neuroscience Centre, University of Galway, Galway, Ireland; Centre for Pain Research, University of Galway, Galway, Ireland; Department of Physiology, School of Medicine, Autonomous University of Madrid, Madrid, Spain. Electronic address:
Over 40% of neuropathic pain patients experience mood and cognitive disturbances, often showing reduced response to analgesics, with most affected individuals being female. This highlights the critical role of biological sex in pain-related affective and cognitive disorders, making it essential to understand the emotional and cognitive circuits linked to pain for improving treatment strategies. However, research on sex differences in preclinical pain models is lacking.
View Article and Find Full Text PDFPLoS One
November 2024
Dongnam Esoo Korean Medical Clinic, Cheongju-si, Republic of Korea.
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