Influence of the vanilloid receptor TRPV1 on the activation of spinal cord glia in mouse models of pain

• Published in: Experimental neurology Vol. 220; no. 2; pp. 383 - 390
• Main Authors: Chen, Yong, Willcockson, Helen H., Valtschanoff, Juli G.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.12.2009; Elsevier
• Subjects: Animals; Arthritis, Experimental - pathology; Astrocytes; Behavior, Animal - physiology; Biological and medical sciences; Biomarkers; Glia; Glial Fibrillary Acidic Protein - genetics; Glial Fibrillary Acidic Protein - metabolism; Hyperalgesia - genetics; Hyperalgesia - pathology; Hyperalgesia - psychology; Immunohistochemistry; Inflammation - chemically induced; Inflammation - genetics; Inflammation - pathology; Injuries of the nervous system and the skull. Diseases due to physical agents; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Microglia; Mouse; Neuroglia - physiology; Neurology; Pain - genetics; Pain - pathology; Pain - psychology; Peripheral Nerves - pathology; Peripheral Nervous System Diseases - chemically induced; Peripheral Nervous System Diseases - pathology; Spinal cord; Spinal Cord - pathology; Traumas. Diseases due to physical agents; TRPV Cation Channels - genetics; TRPV Cation Channels - physiology; TRPV-1; TRPV-1; Spinal cord; Mouse; Glia; Astrocytes; Microglia; Animal model; Nervous system diseases; Neuroglia; Rodentia; Central nervous system; Astrocyte; Vertebrata; TRPV1 vanilloid receptor; Mammalia; Pain; Animal
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2009.09.030

Although activation of spinal glia has been implicated in the development of pathological pain, the mechanisms underlying glial activation are not fully understood. One such mechanism may be triggered by reaction to neuroactive substances released from central axons of sensory afferents. The vanilloid receptor TRPV1, a nonselective cation channel in nociceptive sensory afferents, mediates the release of neurotransmitters, such as glutamate and CGRP in the dorsal horn, which can subsequently activate glia. To test the hypothesis that activation of spinal glia is mediated, at least in part, by TRPV1, we studied the expression of markers for microglia (ionized calcium-binding adapter molecule 1, Iba1) and astrocytes (glial fibrillary acidic protein, GFAP) in the spinal cord of TRPV1 knockout mice (KO) vs. wild-type mice (WT) in models of acute (intraplantar capsaicin), inflammatory (adjuvant-induced arthritis, AIA), and neuropathic pain (partial sciatic nerve ligation, PSNL). We found that (i) naïve KO mice had denser immunostaining for both Iba1 and GFAP than naive WT mice; (ii) the immunostaining for Iba1 increased significantly in treated mice, compared to naïve mice, 3 days after capsaicin and 7–14 days after AIA or PSNL, and was significantly greater in WT than in KO mice 3 days after capsaicin, 7–14 days after AIA, and 7 days after PSNL; and iii) the immunostaining for GFAP increased significantly in treated mice, compared to naïve mice, 3 days after capsaicin and 14–21 days after AIA or PSNL, and was significantly greater in WT than in KO mice 14 days after AIA or PSNL. Our results suggest that TRPV1 plays a role in the activation of spinal glia in mice with nociceptive, inflammatory, and neuropathic pain.