期刊
EXPERIMENTAL NEUROLOGY
卷 184, 期 1, 页码 162-168出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/S0014-4886(03)00102-X
关键词
adenosine; neutrophil; inflammation; neuroimmunology; cell trafficking; rodent
资金
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR045282] Funding Source: NIH RePORTER
- NIAMS NIH HHS [R01AR45282] Funding Source: Medline
Spinal administration of adenosine inhibits neutrophil accumulation in skin. The neural pathways mediating this action are unknown. We investigated individually the roles of capsaicin sensitive primary afferent fibers, sympathetic efferent fibers, and dorsal roots in this regulation. One week after implantation of intrathecal (IT) catheters into rats, the adenosine receptor agonist cyclohexyladenosine (CHA) or vehicle was injected intrathecally. Inflammatory skin lesions were induced by intradermal carrageenan. Three hours later, skin was harvested and assayed for neutrophils by measuring myeloperoxidase (MPO) activity. Intrathecal CHA (5 mug/kg) decreased neutrophil infiltration into skin lesions. Nociceptive peptides were largely depleted from central terminals of primary afferents by IT capsaicin pretreatment. This depletion had no effect on either basal neutrophil infiltration or CHA-mediated modulation. Sympathetic fibers were largely destroyed by systemic 6-hydoxydopamine (6-OHDA) pretreatment; sympathectomy did not affect basal neutrophil infiltration or block its suppression by IT CHA. Thus, spinal adenosine effects on skin neutrophil trafficking appear to be independent of sympathetic nerves and primary afferent peptides, although incomplete lesions by chemical pretreatments may have confounded our results. Sensory fibers were interrupted by prior unilateral dorsal rhizotomies. This procedure had no effect on neutrophil accumulation in control rats. However, rhizotomy blocked the CHA effect, with MPO levels 45 +/- 18% greater in denervated than control skin in IT CHA-treated animals (P < 0.05). It is clear that the spinal adenosine effect requires intact somatic connectivity. Information on pain and inflammation in the periphery is transmitted to the nervous system, where increased spinal adenosine levels can suppress peripheral inflammation. (C) 2003 Elsevier Science (USA). All rights reserved.
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