Role of spinal Cav2.2 and Cav2.1 ion channels in bladder nociception.
OBJECTIVE
High voltage activated calcium channels have been implicated in nociceptive transmission in several animal pain models. To our knowledge this is the first study to evaluate the ability of various high voltage activated calcium channel blockers to inhibit the transmission of noxious stimuli from the bladder at the level of the spinal cord.


METHODS
The nociceptive response was measured by analyzing the visceromotor reflex and cardiovascular (pressor) responses to bladder distention. The role of Cav2.2 (N-type), Cav2.1 (P/Q-type) and Cav1 (L-type) calcium channels in bladder nociceptive reflex responses was examined using omega-conotoxin-GVIA, omega-agatoxin IVA/omega-conotoxin MVIIC and verapamil (Sigma-Aldrich), respectively. Female Sprague-Dawley rats were acutely instrumented with intrathecal catheters, carotid arterial and bladder cannulas. Needle electrodes were placed directly into the abdominal musculature to measure myoelectric activity subsequent to repeat phasic bladder distention at 60 mm Hg for 30 seconds at 3-minute intervals with the rats under 1% isoflurane. Drugs were administered by intrathecal injection 2 minutes before distention and responses were recorded for 15 minutes per dose.


RESULTS
When administered intrathecally, omega-conotoxin-GVIA and omega-conotoxin MVIIC (10 microg/kg each) significantly attenuated reflex responses to noxious bladder distention to 12% and 65% of the maximal visceromotor reflex response, and to 45% and 59% of the control pressor response, respectively. However, agatoxin and verapamil were less effective.


CONCLUSIONS
The study suggests that spinal Cav2.2 and Q-type Cav2.1 calcium channels contribute to acute bladder nociception, while Cav1 channels have a limited role.
Su
Xin
X
Department of Urology, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939, USA. xin.2.su@gsk.com
Leon
Lisa A
LA
Laping
Nicholas J
NJ
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000502:physiology*; D020916:Conotoxins / Q000494:pharmacology; D005260:Female; D009619:Nociceptors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology; D001743:Urinary Bladder / Q000502:physiology*; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020916:Conotoxins; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA; C503279:Cacna1b protein, rat; C085882:omega-conotoxin MVIID