TY - JOUR
T1 - Double and triple spikes in C-nociceptors in neuropathic pain states: An additional peripheral mechanism of hyperalgesia
AU - Serra, Jordi
AU - Sol, Rom
AU - Aleu, Jordi
AU - Quiles, Cristina
AU - Navarro, Xavier
AU - Bostock, Hugh
PY - 2011/2/1
Y1 - 2011/2/1
N2 - It was previously reported that in 5 patients with small-fiber neuropathy, neuropathic pain, and hyperalgesia, application of a single, brief electrical stimulus to the skin could give rise to 2 afferent impulses in a C-nociceptor fiber. These double spikes, which are attributed to unidirectional conduction failure at branch points in the terminal arborisation, provide a possible mechanism for hyperalgesia. We here report that similar multiple spikes are regularly observed in 3 rat models of neuropathic pain: nerve crush, nerve suture, and chronic constriction injury. The proportion of nociceptor fibers exhibiting multiple spikes was similar (10.1-18.5%) in the 3 models, and significantly greater than the proportion in control (unoperated) animals (1.2%). As in the human patients, multiple spikes in the rat models were often provoked by increasing the stimulation rate from 0.25 to 2 Hz, but provocation by warming was less consistent. Multiple spiking was also directly dependent on stimulus intensity, consistent with a mechanism that depends on activation of multiple branches. Whereas only double spikes had previously been described in patients, in these more extensive recordings from rats we found that triple spikes could also be observed after a single electrical stimulus. The results strengthen the suggestion that multiple spiking, because of impaired conduction in the terminal branches of nociceptors, may contribute to hyperalgesia in patients with neuropathic pain. Double and triple spikes in c-nociceptors, caused by impaired conduction in terminal branches, may be an important cause of hyperalgesia in patients with neuropathic pain. © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
AB - It was previously reported that in 5 patients with small-fiber neuropathy, neuropathic pain, and hyperalgesia, application of a single, brief electrical stimulus to the skin could give rise to 2 afferent impulses in a C-nociceptor fiber. These double spikes, which are attributed to unidirectional conduction failure at branch points in the terminal arborisation, provide a possible mechanism for hyperalgesia. We here report that similar multiple spikes are regularly observed in 3 rat models of neuropathic pain: nerve crush, nerve suture, and chronic constriction injury. The proportion of nociceptor fibers exhibiting multiple spikes was similar (10.1-18.5%) in the 3 models, and significantly greater than the proportion in control (unoperated) animals (1.2%). As in the human patients, multiple spikes in the rat models were often provoked by increasing the stimulation rate from 0.25 to 2 Hz, but provocation by warming was less consistent. Multiple spiking was also directly dependent on stimulus intensity, consistent with a mechanism that depends on activation of multiple branches. Whereas only double spikes had previously been described in patients, in these more extensive recordings from rats we found that triple spikes could also be observed after a single electrical stimulus. The results strengthen the suggestion that multiple spiking, because of impaired conduction in the terminal branches of nociceptors, may contribute to hyperalgesia in patients with neuropathic pain. Double and triple spikes in c-nociceptors, caused by impaired conduction in terminal branches, may be an important cause of hyperalgesia in patients with neuropathic pain. © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
KW - Action potential
KW - Allodynia
KW - Animal models
KW - Hyperalgesia
KW - Microneurography
KW - Pain
U2 - 10.1016/j.pain.2010.10.039
DO - 10.1016/j.pain.2010.10.039
M3 - Article
SN - 0304-3959
VL - 152
SP - 343
EP - 353
JO - Pain
JF - Pain
IS - 2
ER -