Spinal CCL2 pronociceptive action is no longer effective in CCR2 receptor antagonist-treated rats
| Autor: | Philippe Sarret, William Rostène, Stéphane Mélik-Parsadaniantz, Patricia Mechighel, Patrick Kitabgi, Romain-Daniel Gosselin, Nicolas Beaudet, Marc-André Dansereau, Michel Pohl, Annie Mauborgne, Blandine Pommier |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Pain Threshold medicine.medical_specialty Pyrrolidines Receptors CCR2 medicine.drug_class Calcitonin Gene-Related Peptide Central nervous system TRPV Cation Channels Enzyme-Linked Immunosorbent Assay Substance P Calcitonin gene-related peptide Biochemistry Potassium Chloride Rats Sprague-Dawley Cellular and Molecular Neuroscience chemistry.chemical_compound Ganglia Spinal Internal medicine medicine Animals Neurons Afferent Chemokine CCL2 Analysis of Variance Behavior Animal business.industry Chronic pain medicine.disease Receptor antagonist Spinal cord Rats medicine.anatomical_structure Endocrinology Gene Expression Regulation Spinal Cord chemistry Hyperalgesia Capsaicin Neuropathic pain Calcium Neuron business Subcellular Fractions |
| Zdroj: | Journal of Neurochemistry. 106:757-769 |
| ISSN: | 1471-4159 0022-3042 |
| DOI: | 10.1111/j.1471-4159.2008.05429.x |
| Popis: | A better understanding of the mechanisms linked to chemokine pronociceptive effects is essential for the development of new strategies to better prevent and treat chronic pain. Among chemokines, MCP-1/CCL2 involvement in neuropathic pain processing is now established. However, the mechanisms by which MCP-1/CCL2 exerts its pronociceptive effects are still poorly understood. In the present study, we demonstrate that MCP-1/CCL2 can alter pain neurotransmission in healthy rats. Using immunohistochemical studies, we first show that CCL2 is constitutively expressed by primary afferent neurons and their processes in the dorsal horn of the spinal cord. We also observe that CCL2 is co-localized with pain-related peptides (SP and CGRP) and capsaicin receptor (VR1). Accordingly, using in vitro superfusion system of lumbar dorsal root ganglion and spinal cord explants of healthy rats, we show that potassium or capsaicin evoke calcium-dependent release of CCL2. In vivo, we demonstrate that intrathecal administration of CCL2 to healthy rats produces both thermal hyperalgesia and sustained mechanical allodynia (up to four consecutive days). These pronociceptive effects of CCL2 are completely prevented by the selective CCR2 antagonist (INCB3344), indicating that CCL2-induced pain facilitation is elicited via direct spinal activation of CCR2 receptor. Therefore, preventing the activation of CCR2 might provide a fruitful strategy for treating pain. |
| Databáze: | OpenAIRE |
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