Pain
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Clinical Trial
Assessment of the reproducibility of intradermal administration of capsaicin as a model for inducing human pain.
The reproducibility and tolerability of intradermal (i.d.) administration of capsaicin as a method for eliciting human pain was assessed in healthy male volunteers (n = 12). The primary endpoints for assessing pain were spontaneous pain response and areas of allodynia, pinprick hyperalgesia and neurogenic inflammation. These were recorded before, immediately after, and at regular intervals following each of four doses (250 microg) of capsaicin (two per trial day). ⋯ A positive correlation was found between the area of allodynia and area of pinprick hyperalgesia (r(2) = 0.835). Overall, the model was well tolerated with no reports of adverse events. We conclude that the tolerability profile, and variability of i.d. capsaicin-induced pain is acceptable for pharmacological profiling of novel anti-nociceptive agents, with limited number of subjects.
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Comparative Study
Inward currents in primary nociceptive neurons of the rat and pain sensations in humans elicited by infrared diode laser pulses.
Radiant heat is often used to study nociception in vivo. We now used infrared radiation generated by a diode laser stimulator (wavelength 980 nm) to investigate transduction mechanisms for noxious heat stimuli in acutely dissociated dorsal root ganglion (DRG) neurons of rats in vitro. The laser stimulator offered the unique opportunity to test whether the same stimuli also elicit pain sensations in humans. ⋯ No significant differences were seen between the pain thresholds in hairy and in glabrous skin, probably due to the deep penetration of this laser radiation. The mean pain threshold for stimuli > or =200 ms in humans was 2.5 +/- 0.2 J mm(-2) (n = 11), and did not differ from the thresholds for the induction of I(heat) in vitro. Our results indicate that I(heat) in primary sensory neurons can be activated by infrared laser pulses that are painful in humans.
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Facial expression of pain has rarely been researched in the context of facial expression of negative emotions with which it may occur. The main aim of the study was to investigate how pain expression resembled or differed from that of other negative emotions (fear, anger, sadness, surprise, disgust and embarrassment), using multidimensional scaling, a dimensional approach to understanding relationships among emotions. As possible misidentification of facial expressions by participants could distort those results, a judgement study as a categorical approach was conducted to examine the accuracy of identification of pain and negative emotion facial expressions. ⋯ Confidence in ratings approximated accuracy of identification. Multidimensional scaling revealed two dimensions: the first distinguished embarrassment from all other emotion expressions; the second separated pain, sadness and anger from fear, surprise and disgust. Possible explanations for these findings were sought in patterns of facial action units, and in the messages conveyed by the expressions according to Fridlund's Behavioural Ecology View.
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Injury to peripheral dental tissues evokes dynamic alternations in central sensory pathways. We have previously reported that transient stimulation of the dental pulp with noxious heat evokes the induction of the immediate early gene product Fos in the transitional region between subnucleus interpolaris and caudalis (Vi/Vc) and subnucleus caudalis (Vc). A question arises as to whether similar changes occur in response to inflammation to the tooth pulp. ⋯ The number of Fos-positive neurons was greater in the trigeminal subnucleus caudalis (Vc) and the transitional regions (Vi/Vc) in LPS-treated animals compared with sham-operated animals, and greater in the deeper laminae than the superficial laminae of each trigeminal region. LPS treatment did not evoke Fos expression in the rostral trigeminal regions above Vi/Vc. These results demonstrate that LPS-induced pulpal inflammation results in significant alterations in the Vi/Vc and Vc, and such changes may underlie the observed nociceptive behavioral responses and may play an important role in producing a symptomatic pulpitis in humans.
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Comparative Study
Micromolar lidocaine selectively blocks propagating ectopic impulses at a distance from their site of origin.
Abnormal impulses caused by very slowly inactivating Na channels of peripheral nerve have been proposed to play a critical role in neuropathic pain. Low concentrations of local anesthetics, often effective in treating experimental and clinical neuropathic pain, are also known to potently suppress the long after-depolarizations induced by these persistently open Na channels. However, these drug actions on impulses that have propagated away from such sites are undetermined. ⋯ Tetrodotoxin also inhibited the induced spontaneous activity, but only at concentrations that also depressed the compound action potential spike. These findings show that low concentrations of lidocaine can restore normal firing patterns in nerve where hyperexcitability has been caused by delayed Na-channel inactivation, without acting directly at the site where ectopic impulses are generated. Thus, it appears that the pattern of abnormal activity rather than an abnormally gating Na channel per se can be a target for lidocaine's therapeutic action.