To examine the role of mGluR1 (a subunit of the group I metabotropic glutamate receptor) in the nociceptive responses of rats following a subcutaneous injection of formalin into the plantar surface of the hind paw, we delivered antisense oligonucleotides (ODNs) against mGluR1 into the rat lumbar spinal cord (L3-L5) intrathecally using an HVJ-liposome-mediated gene transfer method. Rats treated with a single injection of mGluR1 antisense ODNs into the intrathecal space of the lumbar spinal cord showed a marked reduction of the early-sustained phase of formalin-induced nociceptive responses, but not of their acute phase. The reduction of nociceptive behavioral responses became apparent at day 2 after the antisense treatment and lasted for 2 days. This corresponded to a long-lasting down-regulation (46%) of mGluR1 expression in the lumbar cord. This down-regulated mGluR1 was observed at day 2 and persisted until day 4 after the intrathecal infusion of mGluR1 antisense ODN. In contrast, rats treated with mGluR1 sense or mismatch ODNs showed none of these changes. These results suggest that mGluR1 may play a crucial role in the sustained nociception of formalin-induced behavioral responses.
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http://dx.doi.org/10.1016/s0006-8993(03)03330-4 | DOI Listing |
Cell Mol Neurobiol
January 2025
Department of Neurology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
Neuropathic pain, a prevalent complication following spinal cord injury (SCI), severely impairs the life quality of patients. No ideal treatment exists due to incomplete knowledge on underlying neural processes. To explore the SCI-induced effect on nociceptive circuits, the protein expression of c-Fos was analyzed as an indicator of neuronal activation in a rat contusion model exhibiting below-level pain.
View Article and Find Full Text PDFJ Pain Res
January 2025
Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu, Korea.
Background: The tooth exhibits increased sensitivity to noxious stimuli due to the dense innervation of thin myelinated Aδ fibers and unmyelinated C fibers within the dental pulp. While prior research has identified dynorphin expression in layers I-II of the dorsal horn across the spinal cord in various pain models, its functional role in trigeminal nociception, including tooth pain, remains underexplored. This study examines the potential role of dynorphin in the nociceptive processing of dental stimuli.
View Article and Find Full Text PDFNeuropharmacology
January 2025
Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229, USA. Electronic address:
Kappa opioid receptors (KOR) expressed by peripheral pain-sensing neurons (nociceptors) are a promising target for development of effective and safer analgesics for inflammatory pain that are devoid of central nervous system adverse effects. Here we sought to delineate the signaling pathways that underlie peripheral KOR-mediated antinociception in adult male and female Sprague-Dawley rats. In an inflammatory model of pain, local intraplantar (i.
View Article and Find Full Text PDFBioorg Chem
January 2025
School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China. Electronic address:
An alternative approach for the management of acute and chronic pains involves prolonging the half-life of endogenous opiates, such as enkephalins that are released in response to nociceptive stimuli. This can be achieved through the inhibition of enzymatic pathways responsible for the hydrolysis of these peptides, particularly targeting Aminopeptidase N (APN) and Neutral Endopeptidase (NEP). In this study, we designed and synthesized a series of dual enkephalinase inhibitors (DENKIs) targeting both APN and NEP as novel analgesic treatments.
View Article and Find Full Text PDFHeliyon
January 2025
Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand.
Transient Receptor Potential (TRP) channels are a family of ion channels that play pivotal roles in various physiological processes, including sensory transduction, temperature regulation, and inflammation. In the context of dentistry, recent research has highlighted the involvement of TRP channels in mediating sensory responses and inflammation in dental tissues and temporo-mandibular joint (TMJ) structure. TRP channels have emerged as major contributors in the development of inflammatory conditions and pain affecting the oral cavity and related structures, such as periodontitis, dental erosion cause hypersensitivity, pulpitis, and TMJ disorders.
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