Articles: hyperalgesia.
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Activation of A1 adenosine receptors (A1Rs) causes antinociception after nerve injury and inflammation. However, the role of A2a adenosine receptors (A2aRs) for pain processing is less clear. In the current study, the authors investigated the role of spinal adenosine A1Rs and A2aRs for the maintenance of mechanical hyperalgesia in an animal model for postoperative pain. ⋯ Spinal A1Rs but not A2aRs play an important role in the maintenance of nonevoked and evoked pain behaviors after an incision. Furthermore, A1R-induced spinal antinociception is mediated by interactions with pertussis toxin-sensitive G proteins. In addition, the opening of adenosine triphosphate-sensitive K channels but not of calcium-activated potassium channels and voltage-gated Kv1.3 or Kv1.6 channels contribute to the antinociceptive effect of A1R agonists.
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Endometriosis (ENDO) is a painful disorder defined by extrauteral endometrial growths. It is created in rats by autotransplanting pieces of uterus (which form cysts), or, for shamENDO, fat (no cysts). ENDO induces vaginal hyperalgesia, likely via central sensitization. ⋯ We predicted that the opposing influences of estradiol on ENDO- and OVX-induced hyperalgesia would cancel each other. As predicted, OVX had no effect on ENDO-induced hyperalgesia and estradiol replacement alleviated it. These results suggest that, in intact rats, ENDO-induced vaginal hyperalgesia is exacerbated by estradiol, and that different mechanisms underlie ENDO-induced versus OVX-induced vaginal hyperalgesia.
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Randomized Controlled Trial Clinical Trial
Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers.
Although the preclinical literature suggests that cannabinoids produce antinociception and antihyperalgesic effects, efficacy in the human pain state remains unclear. Using a human experimental pain model, the authors hypothesized that inhaled cannabis would reduce the pain and hyperalgesia induced by intradermal capsaicin. ⋯ This study suggests that there is a window of modest analgesia for smoked cannabis, with lower doses decreasing pain and higher doses increasing pain.
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Dysmenorrhoea patients experience intense visceral pain during menstruation. Recurrent and/or intense visceral pain can induce facilitation of somatic and visceral nociceptive processing which can lead to viscero-somatic (referred) and viscero-visceral hyperalgesia. Our aim was to study if dysmenorrhoea is associated with hypersensitivity in the referred somatic skin area or in the large bowel, i.e., viscero-visceral hyperalgesia. ⋯ There were no differences in compliance between the groups. These findings suggest that, despite the absence of overt gastro-intestinal symptoms or viscero-somatic sensitisation, dysmenorrhoea patients demonstrate intestinal hypersensitivity. This can be regarded as the result of centrally mediated viscero-visceral hyperalgesia due to recurrent intense menstrual pain.
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Randomized Controlled Trial
The effects of the TRPV1 antagonist SB-705498 on TRPV1 receptor-mediated activity and inflammatory hyperalgesia in humans.
TRPV1 is a cation channel activated by a range of noxious stimuli and highly expressed in nociceptive fibres. TRPV1 receptors are involved in pain and sensitisation associated with tissue injury and inflammation; hence, TRPV1 antagonists are potentially useful for the treatment of such pain states. SB-705498 is a potent, selective and orally bioavailable TRPV1 antagonist with demonstrated efficacy in a number of preclinical pain models. ⋯ The magnitude of the pharmacodynamic effects of SB-705498 appeared to be related to plasma concentration. These results indicate that SB-705498, at a clinically safe and well-tolerated dose, has target-specific pharmacodynamic activity in humans. These data provide the first clinical evidence that a TRPV1 antagonist may alleviate pain and hyperalgesia associated with inflammation and tissue injury.