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Potentiation of Clonidine Analgesia in Rats Deleted of TRPV1‐Expressing Afferent Neurons
Author(s) -
Pan HuiLin,
Pan HaoMin,
Richardson Timothy,
Chen ShaoRui
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1176-c
Subject(s) - clonidine , trpv1 , resiniferatoxin , spinal cord , agonist , nociception , chemistry , endocrinology , nociceptor , medicine , pharmacology , anesthesia , receptor , transient receptor potential channel , psychiatry
The α2‐adrenergic receptors (α2‐ARs) are located on primary afferent terminals and on neurons in the spinal cord dorsal horn. However, their role in the analgesic effect produced by the α2‐AR agonist is not known. In this study, we determined whether removal of presynaptic α2‐ARs on TRPV1‐expressing sensory neurons by resiniferatoxin (RTX) alters the antinociceptive effect of the α2‐AR agonist clonidine. The effect of intrathecal injection of clonidine was measured by testing the paw withdrawal response to noxious mechanical or heat stimuli. In RTX‐treated rats, the α2A‐AR‐immunoreactivity co‐expressed with TRPV1‐expressing terminals in the spinal cord was eliminated. However, the α2C‐AR‐immunoreactivity in the spinal cord was little changed. Surprisingly, intrathecal clonidine produced a much greater increase in the mechanical withdrawal threshold in RTX‐ than in vehicle‐treated rats. The duration of the clonidine effect was also significantly increased in RTX‐treated rats. In the vehicle‐treated group, although intrathecal clonidine produced a large increase in the thermal withdrawal latency, it only had a small and short‐lasting effect on the mechanical withdrawal threshold. Furthermore, the protein kinase Cγ‐immunoreactivity in the superficial dorsal horn was profoundly decreased in RTX‐treated rats. This study provides new information that the antinociceptive effect of spinally administered α2‐AR agonists is largely modality‐specific. Loss of TRPV1‐expressing sensory neurons leads to a reduction in presynaptic α2A‐ARs but paradoxically potentiates the effect of clonidine on mechano‐nociception, possibly by reducing α2‐AR desensitization through protein kinase Cγ.