Articles: hyperalgesia.
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Pregabalin is used for treatment of neuropathic pain conditions. The present study evaluated effects of pregabalin in 2 rat models of muscle-induced hyperalgesia: Inflammatory and noninflammatory. Muscle hyperalgesia (withdrawal threshold to compression of the muscle) and cutaneous hyperalgesia of the paw (withdrawal threshold to von Frey filaments) were measured before and after induction of hyperalgesia and after treatment with pregabalin (saline, 10 to 100 mg/kg i.p.). In the inflammatory model, 3% carrageenan injected into 1 gastrocnemius muscle decreased the mechanical withdrawal threshold of the paw bilaterally and the compression withdrawal threshold of the muscle ipsilaterally 2 weeks later. Pregabalin (10 to 100 mg/kg) increased the compression withdrawal threshold of the inflamed muscle when compared with vehicle controls. Pregabalin also increased the mechanical withdrawal threshold of the paw bilaterally, but only with 100 mg/kg. In the noninflammatory model, 2 unilateral injections of acidic saline into the gastrocnemius muscle produced bilateral cutaneous and muscle hyperalgesia 24 hours after the second injection. Pregabalin (10 to 100 mg/kg i.p.) significantly increased the compression withdrawal thresholds of the muscle and the mechanical withdrawal threshold of the paw bilaterally when compared with vehicle. However, pregabalin also has significant motor effects at the higher doses (60 to 100 mg/kg). Therefore, pregabalin reduces both muscle and cutaneous hyperalgesia that occurs after muscle insult in 2 animal models of muscle pain at doses that do not produce ataxia. ⋯ This study shows that pregabalin reduces both cutaneous and muscle hyperalgesia in inflammatory and noninflammatory models of muscle pain. Thus, pregabalin may be an effective treatment for people with chronic muscle pain.
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About 60% of patients complain of cutaneous allodynia during migraine episodes, often in the periorbitary region of the pain side. Pre-clinical studies have shown that the underlying mechanism is sensitisation of primary nociceptors and central trigeminovascular neurons and that patients have a lower pain threshold for mechanical stimulation compared to controls. The objective of this study was to determine the prevalence of allodynia during headache attacks in different forms of migraine. ⋯ Allodynia was a common complaint in migraineurs, being present in more than 40% patients of each group. A higher frequency was observed in MA and in CM patients. This observation may suggest that both frequency of attacks and presence of aura episodes may contribute to induce changes in neuronal activation threshold thought to sustain allodynia.
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Nitric oxide (NO) and its synthesizing enzymes, including NO synthase-2 (NOS-2, also called inducible NOS, iNOS), have been implicated in spinal nociception. 1400W is a highly selective NOS-2 inhibitor, as compared with either NOS-1 (neuronal NOS, nNOS) or NOS-3 (endothelial NOS). Here we examined the anti-nociceptive effects of intrathecal (IT) administration of 1400W in two experimental models of hyperalgesia (formalin and carrageenan models), in addition to the effect of 1400W on stimulation-induced activation of spinal p38 mitogen-activated protein kinase (p38). IT treatment of rats with 1400W produced a dose-dependent inhibition of paw formalin-induced phase II flinches, and attenuated carrageenan-induced thermal hyperalgesia. ⋯ However, when the protein was immunoprecipitated prior to Western blotting, NOS-2-immunoreactive bands were detected in the tissues, including naïve spinal cords. The presence of constitutive spinal NOS-2 was further confirmed by reverse transcriptase-polymerase chain reaction. Taken together, the present studies suggest that constitutively expressed spinal NOS-2 mediates tissue injury and inflammation-induced hyperalgesia, and that activation of p38 is one of the downstream factors in NO-mediated signaling in the initial processing of spinal nociception.
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Neuroscience research · May 2007
FK506 reduces the severity of cutaneous hypersensitivity in rats with a spinal cord contusion.
Spinal cord injury (SCI) leads to persistent pain as well as motor dysfunction, both of which lack effective therapeutics. The immunosuppressant FK506 (tacrolimus) has been shown to improve behavioral outcome following SCI in rats. Just prior to a mid-thoracic spinal cord contusion injury, rats were injected with either vehicle or FK506 and treatment was continued through the duration of the experiment. ⋯ Neither treated groups demonstrated an improvement in locomotor function. Thus, some SCI-induced pain is mediated by an FK506-sensitive mechanism. The data also suggest that motor and sensory dysfunctions resulting from SCI are mediated by distinct mechanisms, requiring the use of multiple therapeutic interventions.