Upregulation of the T-type calcium current in small rat sensory neurons after chronic constrictive injury of the sciatic nerve.
Recent data indicate that peripheral T-type Ca2+ channels are instrumental in supporting acute pain transmission. However, the function of these channels in chronic pain processing is less clear. To address this issue, we studied the expression of T-type Ca2+ currents in small nociceptive dorsal root ganglion (DRG) cells from L4-5 spinal ganglia of adult rats with neuropathic pain due to chronic constrictive injury (CCI) of the sciatic nerve. In control rats, whole cell recordings revealed that T-type currents, measured in 10 mM Ba2+ as a charge carrier, were present in moderate density (20 +/- 2 pA/pF). In rats with CCI, T-type current density (30 +/- 3 pA/pF) was significantly increased, but voltage- and time-dependent activation and inactivation kinetics were not significantly different from those in controls. CCI-induced neuropathy did not significantly change the pharmacological sensitivity of T-type current in these cells to nickel. Collectively, our results indicate that CCI-induced neuropathy significantly increases T-type current expression in small DRG neurons. Our finding that T-type currents are upregulated in a CCI model of peripheral neuropathy and earlier pharmacological and molecular studies suggest that T-type channels may be potentially useful therapeutic targets for the treatment of neuropathic pain associated with partial mechanical injury to the sciatic nerve.
Jagodic
Miljen M
MM
Department of Anesthesiology, University of Virginia Health System, Mail Box 800710, Charlottesville, VA 22908-0710, USA.
Pathirathna
Sriyani
S
Joksovic
Pavle M
PM
Lee
WooYong
W
Nelson
Michael T
MT
Naik
Ajit K
AK
Su
Peihan
P
Jevtovic-Todorovic
Vesna
V
Todorovic
Slobodan M
SM
D000704:Analysis of Variance; D000818:Animals; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D003250:Constriction; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D005260:Female; D005727:Ganglia, Spinal / Q000473:pathology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009475:Neurons, Afferent / Q000145:classification / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000209:etiology / Q000473:pathology*; D015854:Up-Regulation / Q000502:physiology*
D020747:Calcium Channels, T-Type; D009532:Nickel