Articles: hyperalgesia.
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Evidence suggests that galanin and its receptors including GalR1 are involved in the modulation of nociception. To understand the contributions of this galanin receptor subtype to the analgesic effect of galanin, we systematically examined the nociception phenotype of the GalR1 knockout (KO) mice. (1) Baseline thresholds: Thermal escape latencies and tactile thresholds of the hind paws were not different between the GalR1 KO and wild type (WT) mice. (2) Thermal injury evoked hyperalgesia: Thermal injury (52 degrees C, 45 s) to one hind paw resulted in a reduction in the thermal escape latency as compared to the uninjured paw. The right/left difference score was significantly greater in the KO (5.9 +/- 0.8 s) than for the WT (2.8 +/- 0.7 s) indicating a greater hyperalgesia. (3) Formalin-induced flinching: Formalin paw injection (2.5%/20 microl) produced a two-phase flinching in both GalR1 KO and WT groups, that was detected by an automated flinching sensor device. ⋯ On days 14-21, GalR1 KO animals showed a significant recovery as compared to WT. In summary, GalR1 KO mice showed no difference from WT with respect to acute nociception, but showed a modest tendency towards increased hyperalgesia after tissue injury and inflammation. These results are consistent with a regulatory effect of galanin at GalR1 receptors on nociceptive processing.
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Comparative Study
The ontogeny of neuropathic pain: postnatal onset of mechanical allodynia in rat spared nerve injury (SNI) and chronic constriction injury (CCI) models.
Neuropathic pain is known to occur in children but remains poorly understood and treated. The aim here was to establish a model of neuropathic pain in neonatal and young rodents. In the adult the spared nerve injury (SNI) model produced robust mechanical allodynia measured as a fall in cutaneous sensory threshold to 16% of controls, within one postoperative day and lasting at least 28 days. ⋯ A similar lack of neuropathic pain behaviour in younger animals was observed using the chronic constriction injury (CCI) model, which produced a clear allodynia in adult rats but no change in hindpaw sensitivity when performed at 10 days of age. Mechanical allodynia can be evoked in very young animals with inflammatory pain, so this developmental profile is selective for peripheral neuropathic pain and suggests a remarkable ability in young animals to compensate for the sensory consequences of nerve injury. The results are consistent with human neonatal responses to nerve injury; further study of underlying mechanisms are likely to yield important information about the pathogenesis and treatment of neuropathic pain.
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Randomized Controlled Trial
Pain measurements and side effect profile of the novel cannabinoid ajulemic acid.
Preclinical findings on ajulemic acid (AJA) showed analgesic and anti-allodynic effects without psychoactive properties making it an appealing substance for the treatment of pain. A recently published randomized double-blind crossover clinical trial described the pain-reducing effects and side effect profile of AJA on 21 patients with chronic neuropathic pain. In this report from this same sample the effects of AJA on the mechanical hypersensitivity, on pain, and on psychological and physical performance were further characterized. ⋯ No significant findings were observed regarding psychotropic or physical measurements. Reported subjective side effects were mainly dry mouth, tiredness and dizziness and did not increase with dose elevation. Overall, these study findings indicate that AJA shows pain-reducing effects on patients with chronic neuropathic pain without clinically relevant psychotropic or physical side effects.
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Postoperative pain significantly impacts patient recovery. However, postoperative pain management remains suboptimal, perhaps because treatment strategies are based mainly on studies using inflammatory pain models. We used a recently developed mouse model of incisional pain to investigate peripheral and spinal mechanisms contributing to heat hyperalgesia after incision. ⋯ Finally, heat hyperalgesia after incision was reversed by antagonism of spinal non-NMDA receptors, unlike inflammatory hyperalgesia, which is mediated via NMDA receptors. Thus, TRPV1 is important for the generation of thermal hyperalgesia after incision. Our observations suggest that all experimental pain models may not be equally appropriate to guide the development of postoperative pain therapies.