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This Article Full Text Full Text (PDF) All Versions of this Article: 95/5/3086    most recent 01343.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Chen, S.-R. Articles by Pan, H.-L. Search for Related Content PubMed PubMed Citation Articles by Chen, S.-R. Articles by Pan, H.-L.

Loss of TRPV1-Expressing Sensory Neurons Reduces Spinal µ Opioid Receptors But Paradoxically Potentiates Opioid Analgesia

¹Departments of Anesthesiology and ²Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania

Submitted 20 December 2005; accepted in final form 8 February 2006

Systemic administration of resiniferatoxin (RTX), an ultrapotent capsaicin analogue, removes transient receptor potential vanilloid type 1 (TRPV1)-expressing afferent neurons and impairs thermal but not mechanical nociception in adult animals. In this study, we determined how loss of TRPV1-expressing sensory neurons alters the antinociceptive effect of µ opioids and µ opioid receptors in the spinal cord. The effect of morphine and (D-Ala²,N-Me-Phe⁴,Gly-ol⁵)-enkephalin (DAMGO) was measured by testing the paw mechanical withdrawal threshold in rats treated with RTX or vehicle. RTX treatment deleted TRPV1-immunoreactive dorsal root ganglion neurons and nerve terminals in the spinal dorsal horn. Also the µ opioid receptor immunoreactivity was markedly reduced in the superficial dorsal horn of RTX-treated rats. However, RTX treatment did not affect the dorsal horn neurons labeled with both TRPV1- and µ opioid receptor-immunoreactivity. Surprisingly, intrathecal morphine or DAMGO produced a greater increase in the withdrawal threshold in RTX- than in vehicle-treated rats. The duration of the effect of intrathecal morphine and DAMGO in RTX-treated rats was also profoundly increased. Furthermore, the antinociceptive effect of systemic morphine was significantly potentiated in RTX-treated rats. The B_MAX (but not K_D) of [³H]-DAMGO binding and DAMGO-stimulated [³⁵S]GTPS activity in the dorsal spinal cord were significantly reduced in the RTX group. This study provides novel information that loss of TRPV1 afferent neurons eliminates presynaptic µ opioid receptors present on TRPV1-expressing afferent neurons but paradoxically potentiates the analgesic effect of µ opioid agonists. Mechano-nociception, transmitted through non-TRPV1 sensory neurons, is subject to potent modulation by µ opioid agonists.

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