Neuroscience letters
-
Neuroscience letters · Jul 2005
Effect of the cannabinoid ajulemic acid on rat models of neuropathic and inflammatory pain.
There is increasing evidence that cannabinoid agonists alleviate the abnormal pain sensations associated with animal models of neuropathic and inflammatory pain. However, cannabinoids produce a number of motor and psychotropic side effects. ⋯ In contrast, HU-210, but not ajulemic acid reduced motor performance in the rotarod test. These findings suggest that ajulemic acid reduces abnormal pain sensations associated with chronic pain without producing the motor side effects associated with THC and other non-selective cannabinoid receptor agonists.
-
Neuroscience letters · Jul 2005
Antibody array analysis of peripheral and blood cytokine levels in rats after masseter inflammation.
This study was undertaken to evaluate the changes in cytokine levels in response to orofacial deep tissue inflammation. Inflammation was induced by injecting complete Freund's adjuvant (CFA, 0.05 ml 1:1 oil/saline suspension) into the masseter of the male Sprague-Dawley rat under brief halothane anesthesia. At 30 min, 5 h and 24 h after CFA injection (n = 3-4/time point), tissues were dissected from masseter and total proteins isolated. ⋯ The present results indicate selective localized cytokine responses to masseter inflammation. Although different cytokines exist in the blood, their levels did not mirror, nor did not appear to depend on, the local cytokine levels. The findings provide specific targets for further studying the involvement of cytokines in orofacial inflammation and hyperalgesia.
-
Neuroscience letters · Jul 2005
Effects of selective tumor necrosis factor-alpha inhibition to pain-behavioral changes caused by nucleus pulposus-induced damage to the spinal nerve in rats.
Application of nucleus pulposus to the spinal nerve and displacement of the adjacent nerve results in behavioral changes in rats. It has been reported that treatment with the tumor necrosis factor-alpha (TNFalpha) inhibitor, infliximab, significantly reduces spontaneous pain behavior in this animal model. However, there have been no reports of the effects of infliximab on mechanical or thermal hyperalgesia using this model. ⋯ Thermal nociceptive thresholds were tested using a sensitive thermal testing device. While disk incision with displacement surgery rats showed mechanical and thermal hyperalgesia after surgery on the experimental side, neither rats treated with infliximab nor the sham operation controls showed these effects. Injection of infliximab seemed to prevent mechanical and thermal hyperalgesia caused by the combination of disk incision and nerve displacement.
-
Neuroscience letters · Jun 2005
Activation of spinal extracellular signaling-regulated kinases by intraplantar melittin injection.
Intraplantar injection of melittin, a major toxic peptide of whole bee venom, has been proved to cause alteration in both behavioral and spinal neuronal responses in rats. To see whether extracellular signaling-regulated kinases (ERK) in the spinal cord dorsal horn are activated and involved in induction and maintenance of persistent ongoing nociception, pain hypersensitivity and inflammation, three doses of U0126 (1,4-diamino-2,3-dicyano-1, 4-bis-[o-aminophenylmercapto]butadiene), a widely used specific MAP kinase kinase (MEK) inhibitor, were administered through chronic intrathecal catheterization prior to or after intraplantar injection of melittin. We found that: (1) the induction of melittin-induced persistent spontaneous nociception (PSN), mechanical and heat hypersensitivity could be suppressed by U0126 in a dose-related manner; (2) specific inhibition of ERK pathway suppressed the maintenance of melittin-induced PSN and heat hypersensitivity, while established mechanical hypersensitivity could not be reversed; and (3) intrathecal administration of U0126 had no effects on peripheral inflammation induced by melittin. This result suggests that spinal ERK pathway might be a common factor involved in inducing and maintaining pathophysiological processes of ongoing pain and heat hyperalgesia, while the role of ERK pathway in generation of the mechanical hypersensitivity is not consistent and remains to be further clarified.
-
Neuroscience letters · Jun 2005
Multiple kinase pathways mediate the early sciatic ligation-associated activation of CREB in the rat spinal dorsal horn.
Phosphorylation of the cyclic AMP response element-binding protein (CREB) in the spinal dorsal horn may critically contribute to chronic pain following peripheral nerve injury. We employed inhibitors and activators of protein kinase A (PKA), protein kinase C (PKC), extracellular signal-regulated kinase 1 and 2 (ERK1/2) and calcium/calmodulin-dependent kinase II (CaMKII) to examine whether these kinases individually or in concert mediate the increase in CREB phosphorylation that is evident as early as 2 h after loose ligation of the sciatic nerve. Specific inhibitors of each kinase significantly attenuated the ligation-associated CREB phosphorylation when compared to saline-treated animals. ⋯ Significant increases in ERK1/2 phosphorylation were also detected 2 h after sciatic ligation confirming a role for the ERK pathway in injury-related responses in the dorsal horn. Each kinase inhibitor significantly attenuated the ligation-associated activation of ERK1/2 as well. These data suggest that early, sciatic ligation-elicited phosphorylation of CREB in the spinal dorsal horn is mediated by multiple kinase pathways, and that PKA, PKC and CaMKII activate CREB at least in part by way of the ERK pathway.