Journal article
Activation of the cAMP transduction cascade contributes to the mechanical hyperalgesia and allodynia induced by intradermal injection of capsaicin
British journal of pharmacology, Vol.122(6), pp.1165-1173
11/13/1997
DOI: 10.1038/sj.bjp.0701486
PMCID: PMC1565045
PMID: 9401782
Abstract
The spinal role of the cAMP transduction cascade in nociceptive processing was investigated in awake behaving rats (male, Sprague-Dawley) by activating or inhibiting this pathway spinally. Microdialysis fibres were implanted into the dorsal horn to infuse drugs directly to the spinal cord.
Animals, without peripheral tissue injury, were tested for responses to repeated applications (10 trials) of von Frey filaments and threshold to mechanical stimulation before and after infusion of 8-bromo-cAMP. In this group of animals treated spinally with 8-br-cAMP (1–10 m
M
) a dose-dependent hyperalgesia and allodynia were produced. This was manifested as an increased number of responses to 10 trials of von Frey filaments (10, 50, 150, 250 m
N
) and a decrease in mechanical threshold.
A second series of experiments studied the manipulation of the cAMP pathway spinally in a model of tissue injury induced by intradermal injection of capsaicin. Animals were either pre- or post-treated spinally with the adenylate cyclase inhibitor, tetrahydrofuryl adenine (THFA) or the protein kinase A inhibitor, myrosilated protein kinase (14–22) amide (PKI). Injection of capsaicin resulted in an increased number of responses to repeated applications of von Frey filaments and a decrease in threshold to mechanical stimuli outside the site of injection, secondary mechanical hyperalgesia and allodynia.
Pre-treatment with either THFA (1 m
M
) or PKI (5 m
M
) had no effect on the capsaicin-evoked secondary hyperalgesia and allodynia.
In contrast, post-treatment spinally with THFA (0.01–1 m
M
) or PKI (0.05–50 m
M
) dose-dependently reduced the mechanical hyperalgesia and allodynia produced by capsaicin injection. Furthermore, the mechanical hyperalgesia and allodynia blocked by the adenylate cyclase inhibitor, THFA (1 m
M
), was reversed by infusion of 8-bromo-cAMP (0.01–10 m
M
) in a dose-dependent manner.
Thus, this study demonstrates that activation of the cAMP transduction cascade at the spinal cord level results in mechanical hyperalgesia and allodynia and that the secondary mechanical hyperalgesia and allodynia following intradermal injection of capsaicin is mediated by this same transduction cascade.
Details
- Title: Subtitle
- Activation of the cAMP transduction cascade contributes to the mechanical hyperalgesia and allodynia induced by intradermal injection of capsaicin
- Creators
- Kathleen A Sluka - Physical Therapy Graduate Program, College of Medicine, University of Iowa, 2600 Steindler Building, Iowa City, IA 52242, U.S.A
- Resource Type
- Journal article
- Publication Details
- British journal of pharmacology, Vol.122(6), pp.1165-1173
- DOI
- 10.1038/sj.bjp.0701486
- PMID
- 9401782
- PMCID
- PMC1565045
- ISSN
- 0007-1188
- eISSN
- 1476-5381
- Language
- English
- Date published
- 11/13/1997
- Academic Unit
- Iowa Neuroscience Institute; Nursing; Physical Therapy and Rehabilitation Science; Neuroscience and Pharmacology
- Record Identifier
- 9984070454402771
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