Development of purinergic sensitivity in sensory neurons after peripheral nerve injury in the rat.
Purinoceptors are present in the cell bodies as well as in both peripheral and central terminals of many sensory neurons, where they may play a role in sensory transmission, including pain. After peripheral nerve injury at the spinal nerve level, some axotomized afferent neurons develop ongoing discharges (ectopic discharges) that originate in the dorsal root ganglion (DRG). In the present study, we attempted to determine whether or not purinergic sensitivity develops in injured sensory neurons which display ectopic discharges, as well as in silent units. The L(4) and L(5) spinal nerves were ligated in Sprague-Dawley rats. Four to 21 days after the surgery, the DRGs with attached dorsal roots and spinal nerves were removed and ectopic discharges were recorded from teased dorsal root fascicles using an in vitro recording set-up. The results showed that 75.6 and 65.1% of the chronically axotomized DRG neurons displaying ectopic discharges enhanced their activity after application of adenosine 5'-triphosphate (ATP, 1 mM) or alpha,beta-methylene ATP (mATP, 100 microM), respectively. In addition, application of these purinoceptor agonists evoked activity in 7 of 28 axotomized DRG neurons, which did not show ongoing discharges. In contrast, only 1 of 34 DRG neurons acutely isolated from normal rats (no previous spinal nerve ligation) responded to either mATP or ATP. In most of the tested units, mATP-induced enhancement of ectopic discharges was blocked by non-specific P2X receptor antagonists, PPADS or suramin. The data from the present study suggest that purinergic sensitivity develops in DRG neurons after chronic axotomy and that this purinergic sensitivity is likely to be mediated by P2X purinoceptors. This acquired purinergic sensitivity may play an important functional role in the enhancement of ectopic discharges and exacerbation of pain upon sympathetic activation in the neuropathic pain state.
Zhou
J
J
Marine Biomedical Institute and Department of Anatomy and Neurosciences, University of Texas Medical Branch, Galveston, TX 77555-1069, USA.
Chung
K
K
Chung
J M
JM
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D019771:Axotomy; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010525:Peripheral Nerves / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011983:Receptors, Purinergic / Q000502:physiology*
D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate