Articles: hyperalgesia.
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Randomized Controlled Trial
A single dose of gabapentin reduces acute pain and allodynia in patients with herpes zoster.
This randomized, double-blind, placebo-controlled crossover study measured the effect of a single dose of oral gabapentin (900 mg) on pain and allodynia associated with herpes zoster. Pain severity decreased by 66% with gabapentin compared to 33% with placebo. Reductions in allodynia area and severity, and overall pain relief, were also greater with gabapentin.
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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.
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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.
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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.
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Anesthesia and analgesia · Aug 2005
Randomized Controlled Trial Comparative Study Clinical TrialThe short-lasting analgesia and long-term antihyperalgesic effect of intrathecal clonidine in patients undergoing colonic surgery.
In this study, we investigated the antihyperalgesic effect of clonidine after surgery. Sixty patients undergoing right colic resection were studied. Patients were randomized to receive prior to general anesthesia a 2-mL intrathecal (IT) injection of 300 microg of clonidine or saline, or 10 mg of bupivacaine. General anesthesia was achieved using a target concentration propofol infusion and monitored using bispectral index. Postoperative analgesia was provided by morphine IV given through a patient-controlled analgesia device. Postoperative analgesia was assessed by morphine requirements and visual analog scale pain scores at rest, cough, and movement during the first 72 h. Mechanical hyperalgesia was measured by von Frey filaments. Patients were questioned regarding residual pain at 2 wk,1, 6, and 12 mo. The patient-controlled analgesia morphine requirements were significantly smaller in the IT clonidine group (31.5 +/- 12 versus 91 +/- 25.5 and 43 +/- 15 mg, respectively, in groups clonidine, saline, and bupivacaine: P < 0.05 at 72 postoperative hours). The area of hyperalgesia at 72 h was 3 +/- 5 cm(2) in the clonidine group versus 90 +/- 30 and 35 +/- 20 cm(2) in the saline and bupivacaine groups (P < 0.05). At 6 mo, fewer patients in the clonidine group experienced residual pain than in the saline group (0 of 20 versus 6 of 20, P < 0.05). We conclude that both intraoperative spinal clonidine and bupivacaine improve immediate postoperative analgesia. IT clonidine was, however, more potent than IT bupivacaine to reduce postoperative secondary hyperalgesia. ⋯ Spinal clonidine contributes to the reduction of secondary hyperalgesia in patients recovering from abdominal surgery.