Articles: hyperalgesia.
-
Journal of neurochemistry · Aug 2005
Comparative StudyInhibition of p38 mitogen-activated protein kinase attenuates interleukin-1beta-induced thermal hyperalgesia and inducible nitric oxide synthase expression in the spinal cord.
We have reported recently that intrathecal (i.t.) injection of interleukin-1beta (IL-1beta), at a dose of 100 ng, induces inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in the spinal cord and results in thermal hyperalgesia in rats. This study further examines the role of mitogen-activated protein kinase (MAPK) in i.t. IL-1beta-mediated iNOS-NO cascade in spinal nociceptive signal transduction. ⋯ In contrast, both ERK and JNK inhibitor pretreatments only partially (approximately 50%) inhibited the IL-1beta-induced iNOS expression in the spinal cord. Our results suggest that p38 MAPK plays a pivotal role in i.t. IL-1beta-induced spinal sensitization and nociceptive signal transduction.
-
Effects of chronic constriction injury (CCI) and sham surgery of both sciatic nerves were evaluated for reflex lick/guard (L/G) and operant escape responses to thermal stimulation of rats. Experiment 1 compared L/G and escape responses to 0.3 degrees C, 43 degrees C, and 47 degrees C stimulation during a period of 60 days after CCI. Experiment 2 evaluated escape from 44 degrees C, 47 degrees C, and 10 degrees C for 100 days after CCI. The rats escaped from heat or cold stimulation of the paws in a dark compartment by climbing on a thermally neutral platform in a brightly lit compartment. For reflex testing, a single compartment provided no escape option. There was no significant effect of bilateral CCI on reflex or escape responses to nociceptive heat. However, there were long-term increases in the duration of L/G responding during trials of 0.3 degrees C stimulation and in the duration of escape responding to 10 degrees C. Hyperalgesia for cold was confirmed by a preference test, with a 2-compartment shuttle box with one floor heated (45 degrees C) and the other floor cooled (10 degrees C). Occupancy of the heated compartment was significantly increased by CCI (indicating a relative aversion for cold). ⋯ For preclinical testing of treatments for allodynia/hyperalgesia after nerve injury, it is crucial to use methods of testing that are sensitive to effects on nociception throughout the neuraxis. Operant escape testing satisfies this criterion and is sensitive to bilateral CCI of rats, which avoids asymmetric postural/motor influences of unilateral CCI.
-
Ethanol (EtOH) withdrawal increases sensitivity to painful stimuli in adult rats. In this study, withdrawal from a single, acute administration of EtOH dose-dependently produced mechanical allodynia and thermal hyperalgesia in postnatal day 7 (P7) rats. In contrast, P21 rats exhibited earlier and more prolonged mechanical allodynia but not thermal hyperalgesia. For both P7 and P21 rats, blood and spinal cord EtOH levels peaked at 30 minutes after administration, with P7 rats achieving overall higher spinal cord concentrations. Protein kinase C (PKC) has been implicated in mediating pain responses. Inhibitory PKC- and gamma-specific peptides attenuated mechanical allodynia and thermal hyperalgesia in P7 rats, whereas only the PKCgamma inhibitor prevented mechanical allodynia in P21 rats. Immunoreactive PKC in dorsal root ganglion and PKCgamma in lumbar spinal cord increased at 6 hours after EtOH administration in P7 rats. In P21 rats, the density of PKC immunoreactivity remained unchanged, whereas the density of PKCgamma immunoreactivity increased and translocation occurred. These studies demonstrate developmental differences in neonatal nociceptive responses after withdrawal from acute EtOH and implicate a role for specific PKC isozymes in EtOH withdrawal-associated allodynia and hyperalgesia. ⋯ This study examines age-specific nociceptive responses after ethanol exposure by using 2 different ages of rats. The results suggest that ethanol age-dependently alters sensitivity to mechanical and thermal stimuli via specific protein kinase C isozymes. These results begin to ascertain the mechanisms that produce abnormal pain after alcohol exposure.
-
Naunyn Schmiedebergs Arch. Pharmacol. · Aug 2005
Centrally mediated antihyperalgesic and antiallodynic effects of zonisamide following partial nerve injury in the mouse.
Some antiepileptic drugs are used clinically to relieve neuropathic pain. We have evaluated the effects and investigated the possible mechanisms of action of zonisamide, an antiepileptic drug, on thermal hyperalgesia and tactile allodynia in a murine chronic pain model that was prepared by partial ligation of the sciatic nerve. Subcutaneously administered zonisamide (10 and 30 mg/kg) produced antihyperalgesic and antiallodynic effects in a dose-dependent manner; these effects were manifested by elevation of the withdrawal threshold in response to a thermal (plantar test) or mechanical (von Frey) stimulus, respectively. ⋯ Moreover, the nitric oxide synthase inhibitor L-NAME, when injected either i.c.v. or i.t., potentiated the analgesic effects of zonisamide. In contrast, neither i.c.v. nor i.t. zonisamide produced antinociceptive effects against acute thermal and mechanical nociception in non-ligated mice. Together, following peripheral nerve injury, it appears that zonisamide produces centrally mediated antihyperalgesic and antiallodynic effects partly via the blockade of nitric oxide synthesis.
-
Plasma concentrations of soluble tumor necrosis factor alpha (TNF-alpha) receptor type I (sTNF-RI) were assessed in two complex regional pain syndrome (CRPS) patient groups (n = 30 and n = 16) and healthy controls (n = 25). Patients with CRPS and mechanical hyperalgesia had higher levels of sTNF-RI (1,661.8 +/- 146.8 pg/mL) compared with those with CRPS with identical clinical appearance but without hyperalgesia (1,155.9 +/- 56.3 pg/mL) and controls (1,239.5 +/- 42.9 pg/mL). This study suggests involvement of TNF-alpha in mechanical hyperalgesia of CRPS.