TY - JOUR
T1 - The effect of phorbol esters on the responses of primate spinothalamic neurons to mechanical and thermal stimuli
AU - Palecek, J.
AU - Paleckova, V.
AU - Dougherty, P. M.
AU - Willis, W. D.
PY - 1994
Y1 - 1994
N2 - 1. Sensitization of dorsal horn neurons is thought to play an important role in pain perception, secondary hyperalgesia, and abodynia. Recent experimental evidence suggests that the sensitization of dorsal horn neurons is induced by combined increased release of excitatory amino acids and peptides in the spinal cord dorsal horn from nociceptive primary afferents due to an injury-caused barrage of impulses. We tested the hypothesis that protein kinase C (PKC) is involved as a second messenger in this process of neuronal sensitization. To activate PKC, infusion of a phorbol ester [12-O- tetradecanoylphorbol-13-acetate (TPA)] into the dorsal horn through a microdialysis fiber was used. During TPA infusion the background activity of spinothalamic (STT) neurons increased substantially. After TPA application, while the background activity of the STT neurons was still increased, the responses evoked by either innocuous or noxious mechanical stimulation of the cutaneous receptive field did not change from the control level. However, 1 h after TPA administration the background activity returned to the control level and responses to innocuous mechanical stimuli were significantly elevated. The responses of STT cells to noxious heat and noxious mechanical stimuli did not change significantly after TPA administration. When a phorbol ester that does not activate PKC was applied (α-TPA), no significant changes in background or evoked activity of STT cells were observed. Our results provide evidence that PKC may play an important role in the process of sensitization of dorsal horn neurons to innocuous mechanical stimuli.
AB - 1. Sensitization of dorsal horn neurons is thought to play an important role in pain perception, secondary hyperalgesia, and abodynia. Recent experimental evidence suggests that the sensitization of dorsal horn neurons is induced by combined increased release of excitatory amino acids and peptides in the spinal cord dorsal horn from nociceptive primary afferents due to an injury-caused barrage of impulses. We tested the hypothesis that protein kinase C (PKC) is involved as a second messenger in this process of neuronal sensitization. To activate PKC, infusion of a phorbol ester [12-O- tetradecanoylphorbol-13-acetate (TPA)] into the dorsal horn through a microdialysis fiber was used. During TPA infusion the background activity of spinothalamic (STT) neurons increased substantially. After TPA application, while the background activity of the STT neurons was still increased, the responses evoked by either innocuous or noxious mechanical stimulation of the cutaneous receptive field did not change from the control level. However, 1 h after TPA administration the background activity returned to the control level and responses to innocuous mechanical stimuli were significantly elevated. The responses of STT cells to noxious heat and noxious mechanical stimuli did not change significantly after TPA administration. When a phorbol ester that does not activate PKC was applied (α-TPA), no significant changes in background or evoked activity of STT cells were observed. Our results provide evidence that PKC may play an important role in the process of sensitization of dorsal horn neurons to innocuous mechanical stimuli.
UR - http://www.scopus.com/inward/record.url?scp=0028014592&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028014592&partnerID=8YFLogxK
U2 - 10.1152/jn.1994.71.2.529
DO - 10.1152/jn.1994.71.2.529
M3 - Article
C2 - 8176422
AN - SCOPUS:0028014592
SN - 0022-3077
VL - 71
SP - 529
EP - 537
JO - Journal of Neurophysiology
JF - Journal of Neurophysiology
IS - 2
ER -