Pain
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Although activation of alpha(2)-adrenoceptors is known to play an important role in mediating antinociception, the contribution of various alpha(2)-adrenoceptor subtypes in modulating trigeminal nociception remains unknown since subtype specific agonists and antagonists are not available. The present study investigated the functional role of alpha(2)-adrenoceptor subtypes in modulating the N-methyl-D-aspartate-induced nociceptive behavior in the medullary dorsal horn by using antisense oligodeoxynucleotides to selectively knock-down the receptor subtypes. Microinjection of N-methyl-D-aspartate (2 nmol in 10 microl) through a cannula implanted dorsal to the medullary dorsal horn produced a total of 164.9+/-8.8 scratches in the facial region (n=14), and the scratching behavior lasted for 77.8+/-5.2s (n=14). ⋯ Antisense treatment reduced alpha(2A) and alpha(2C) receptor immunoreactivity in the medullary dorsal horn compared to the sense and the vehicle-treated animals. Quantitative image analysis revealed a significant decrease in pixel intensity following the antisense treatment. These results indicate that activation of alpha(2A) adrenoceptor plays an important role in mediating the antinociceptive effect of clonidine in the medullary dorsal horn in the rat.
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Clinicians tend to assign greater weight to non-verbal expression than to patients' self-report when judging the location and severity of pain. Judgments can misrepresent the actual experience because patients can successfully alter their pain expressions. The present research provides a basis for discriminating genuine and deceptive pain expressions by expanding detailed accounts of facial expressions to include previously unexamined variables, including study of temporal patterns and contiguity of facial actions as well as the occurrence of specific deception cues. ⋯ Findings confirmed the difficulty of discriminating the facial expressions, but indicated that faked pain expressions show a greater number of pain-related and non-pain-related actions, have a longer peak intensity and overall duration, and the facial actions observed tend to be less temporally contiguous than are those in genuine pain expressions. The differences between masked pain and neutral expressions were subtle, with a greater frequency of mouth opening and residual eyebrow movement in masked pain expressions. Thus, there is an empirical basis for discriminating genuine and deceptive facial displays.
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Microelectrode recordings of impulse activity in nociceptive C fibres were performed in cutaneous fascicles of the peroneal nerve at the knee level in healthy human subjects. Mechano-heat responsive C units (CMH), mechano-insensitive but heat-responsive (CH) as well as mechano-insensitive and heat-insensitive C units (CM(i)H(i)) were identified. A subgroup of the mechano-insensitive units was readily activated by histamine. ⋯ In conclusion, we have shown that ATP injections at high concentrations activate C-nociceptors in healthy human skin, without preference for mechano-responsive or mechano-insensitive units. ATP did not sensitise human C fibres for mechanical or heat stimuli. We discuss how various mechanisms might contribute to the observed responses to ATP.
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Recent studies indicate that sustained opioid administration produces increased expression of spinal dynorphin, which promotes enhanced sensitivity to non-noxious and noxious stimuli. Such increased "pain" may manifest behaviorally as a decrease in spinal antinociceptive potency. Here, the possibility of similar mechanisms in the antinociception of spinal cannabinoids was explored. ⋯ Daily MK-801 pretreatments, prior to WIN 55,212-2 injection, also produced a significant block of antinociceptive tolerance. These data suggest that like opioids, repeated spinal administration of a cannabinoid CB1 agonist elicits abnormal pain, which results in increased expression of spinal dynorphin. Manipulations that block cannabinoid-induced pain also block the behavioral manifestation of cannabinoid tolerance.
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The spared nerve injury (SNI) model involves a lesion of two of the three terminal branches of the sciatic nerve (tibial and common peroneal nerves) leaving the sural nerve intact. The changes in pain-like sensation of the injured animals appear to correlate with a number of symptoms presented in human patients with neuropathic pain syndromes. In order to characterise the SNI model pharmacologically, reflex nociceptive responses to mechanical and cold stimulation were measured after systemic administration of morphine, mexiletine, gabapentin and the glutamate receptor antagonists, MK-801 and NS1209. ⋯ Gabapentin (100 mg/kg, i.p.) significantly alleviated mechanical allodynia for at least 3h, while no significant effects were observed for either mechanical hyperalgesia or cold allodynia. In contrast, the NMDA receptor antagonist MK-801 (0.1 mg/kg, i.p.) and the AMPA receptor antagonist NS1209 (6 mg/kg, i.p.) did not relieve any of the pain-like behaviours of the SNI animals. The present study has shown that a variety of drugs with proven analgesic potency in other models of chronic pain, have differing analgesic profiles in the SNI model of neuropathic pain.