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Loss of TRPV1-expressing sensory neurons reduces spinal mu opioid receptors but paradoxically potentiates opioid analgesia.
- Source :
-
Journal of neurophysiology [J Neurophysiol] 2006 May; Vol. 95 (5), pp. 3086-96. Date of Electronic Publication: 2006 Feb 08. - Publication Year :
- 2006
-
Abstract
- 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 mu opioids and mu 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 mu 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 mu 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]GTPgammaS 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 mu opioid receptors present on TRPV1-expressing afferent neurons but paradoxically potentiates the analgesic effect of mu opioid agonists. Mechano-nociception, transmitted through non-TRPV1 sensory neurons, is subject to potent modulation by mu opioid agonists.
- Subjects :
- Animals
Behavior, Animal drug effects
Diterpenes administration & dosage
Dose-Response Relationship, Drug
Drug Interactions
Enkephalin, Ala(2)-MePhe(4)-Gly(5)- pharmacokinetics
Fluorescent Antibody Technique methods
Ganglia, Spinal cytology
Gene Expression Regulation drug effects
Gene Expression Regulation physiology
Guanosine 5'-O-(3-Thiotriphosphate) pharmacokinetics
Lectins metabolism
Male
Morphine pharmacology
Neurons, Afferent drug effects
Protein Binding drug effects
Rats
Rats, Sprague-Dawley
Reaction Time drug effects
Spinal Cord metabolism
Sulfur Isotopes pharmacokinetics
TRPV Cation Channels agonists
Tritium pharmacokinetics
Analgesics, Opioid pharmacology
Neurons, Afferent metabolism
Pain Measurement drug effects
Receptors, Opioid, mu metabolism
Spinal Cord cytology
TRPV Cation Channels deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3077
- Volume :
- 95
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of neurophysiology
- Publication Type :
- Academic Journal
- Accession number :
- 16467418
- Full Text :
- https://doi.org/10.1152/jn.01343.2005