TY - JOUR
T1 - Nitro-oleic acid desensitizes TRPA1 and TRPV1 agonist responses in adult rat DRG neurons
AU - Zhang, Xiulin
AU - Koronowski, Kevin B.
AU - Li, Lu
AU - Freeman, Bruce A.
AU - Woodcock, Stephen
AU - de Groat, William C.
PY - 2014/1
Y1 - 2014/1
N2 - Nitro-oleic acid (OA-NO2), an electrophilic fatty acid nitroalkene byproduct of redox reactions, activates transient receptor potential ion channels (TRPA1 and TRPV1) in primary sensory neurons. To test the possibility that signaling actions of OA-NO2 might modulate TRP channels, we examined: (1) interactions between OA-NO2 and other agonists for TRPA1 (allyl-isothiocyanate, AITC) and TRPV1 (capsaicin) in rat dissociated dorsal root ganglion cells using Ca2+ imaging and patch clamp techniques and (2) interactions between these agents on sensory nerves in the rat hindpaw. Ca2+ imaging revealed that brief application (15-30s) of each of the three agonists induced homologous desensitization. Heterologous desensitization also occurred when one agonist was applied prior to another agonist. OA-NO2 was more effective in desensitizing the response to AITC than the response to capsaicin. Prolonged exposure to OA-NO2 (20min) had a similar desensitizing effect on AITC or capsaicin. Homologous and heterologous desensitizations were also demonstrated with patch clamp recording. Deltamethrin, a phosphatase inhibitor, reduced the capsaicin or AITC induced desensitization of OA-NO2 but did not suppress the OA-NO2 induced desensitization of AITC or capsaicin, indicating that heterologous desensitization induced by either capsaicin or AITC occurs by a different mechanism than the desensitization produced by OA-NO2. Subcutaneous injection of OA-NO2 (2.5mM, 35μl) into a rat hindpaw induced delayed and prolonged nociceptive behavior. Homologous desensitization occurred with AITC and capsaicin when applied at 15minute intervals, but did not occur with OA-NO2 when applied at a 30min interval. Pretreatment with OA-NO2 reduced AITC-evoked nociceptive behaviors but did not alter capsaicin responses. These results raise the possibility that OA-NO2 might be useful clinically to reduce neurogenic inflammation and certain types of painful sensations by desensitizing TRPA1 expressing nociceptive afferents.
AB - Nitro-oleic acid (OA-NO2), an electrophilic fatty acid nitroalkene byproduct of redox reactions, activates transient receptor potential ion channels (TRPA1 and TRPV1) in primary sensory neurons. To test the possibility that signaling actions of OA-NO2 might modulate TRP channels, we examined: (1) interactions between OA-NO2 and other agonists for TRPA1 (allyl-isothiocyanate, AITC) and TRPV1 (capsaicin) in rat dissociated dorsal root ganglion cells using Ca2+ imaging and patch clamp techniques and (2) interactions between these agents on sensory nerves in the rat hindpaw. Ca2+ imaging revealed that brief application (15-30s) of each of the three agonists induced homologous desensitization. Heterologous desensitization also occurred when one agonist was applied prior to another agonist. OA-NO2 was more effective in desensitizing the response to AITC than the response to capsaicin. Prolonged exposure to OA-NO2 (20min) had a similar desensitizing effect on AITC or capsaicin. Homologous and heterologous desensitizations were also demonstrated with patch clamp recording. Deltamethrin, a phosphatase inhibitor, reduced the capsaicin or AITC induced desensitization of OA-NO2 but did not suppress the OA-NO2 induced desensitization of AITC or capsaicin, indicating that heterologous desensitization induced by either capsaicin or AITC occurs by a different mechanism than the desensitization produced by OA-NO2. Subcutaneous injection of OA-NO2 (2.5mM, 35μl) into a rat hindpaw induced delayed and prolonged nociceptive behavior. Homologous desensitization occurred with AITC and capsaicin when applied at 15minute intervals, but did not occur with OA-NO2 when applied at a 30min interval. Pretreatment with OA-NO2 reduced AITC-evoked nociceptive behaviors but did not alter capsaicin responses. These results raise the possibility that OA-NO2 might be useful clinically to reduce neurogenic inflammation and certain types of painful sensations by desensitizing TRPA1 expressing nociceptive afferents.
KW - Desensitization
KW - Nitro-oleic acid
KW - Nociception
KW - Primary sensory neuron
KW - TRP channels
UR - http://www.scopus.com/inward/record.url?scp=84888367047&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84888367047&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2013.10.020
DO - 10.1016/j.expneurol.2013.10.020
M3 - Article
C2 - 24212047
AN - SCOPUS:84888367047
SN - 0014-4886
VL - 251
SP - 12
EP - 21
JO - Experimental Neurology
JF - Experimental Neurology
ER -