Pain
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The action of lignocaine on nociceptive transmission in the spinal cord has been studied in vitro using ventral root potential (VRP) recordings from 10-12-day-old rat hemisected spinal cord preparations. Single-shock stimulation of a dorsal root at intensities sufficient to activate high-threshold C-primary afferent fibres elicited VRPs lasting for 15-20 sec in the corresponding ventral root. The VRP consisted of 3 distinct parts: the early, slow and prolonged components, as previously described (Thompson et al. 1992), where the early represents A beta fibre-evoked mono- and polysynaptic responses lasting for tens of milliseconds, the slow is a largely N-methyl-D-aspartic acid (NMDA) receptor-mediated small-calibre afferent-generated component, lasting for about 1.5 sec, and the prolonged is a neurokinin receptor-mediated long-lasting component generated by high-threshold fibres. ⋯ Application of the opiate, glycine, GABAA and GABAB receptor antagonists, naloxone (1 microM), strychnine (100 microM), bicuculline (100 microM) and phaclofen (100 microM) did not alter the depressant effects of lignocaine on the VRP. Low concentrations of lignocaine have a selective action on nociceptive transmission in the spinal cord which is different and more potent than its local anaesthetic conduction blockade in the periphery. This includes a reduction of direct or synaptically driven NMDA- and NK receptor-mediated post-synaptic depolarizations indicating that this class of sodium channel blockers may be potentially useful as analgesic agents, possibly acting on TTX-resistant sodium ion channels.
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Randomized Controlled Trial Comparative Study Clinical Trial
A comparison of morphine, pethidine and fentanyl in the postsurgical patient-controlled analgesia environment.
This study was designed to evaluate whether there is any scientific basis for clinicians' preferences for selecting opioids for use in patient-controlled analgesia (PCA) and to determine whether there are any patients' preferences for being treated with any of these opioids. Results were obtained for 55 postoperative patients recruited to investigate putatively equivalent doses of 3 commonly used opioids--morphine, pethidine and fentanyl--when self-administered postoperatively. No significant differences in the incidence of side effects between groups were found with the exception of more pruritus reported in the group given morphine. ⋯ The majority of patients reported being very satisfied with their postoperative pain management and with PCA, with no differences in satisfaction between the 3 opioid-treated groups. A senior consultant anaesthetist, when asked to make a judgement, was not able to identify which agent each patient was receiving with a better than chance accuracy. These findings suggest that while there may be subtle differences in patient response to these 3 commonly used opioids, none was obviously superior when used for postoperative PCA.
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Comparative Study Clinical Trial Controlled Clinical Trial
A comparison of the effects of noxious and innocuous counterstimuli on experimentally induced itch and pain.
We have studied experimentally induced itch (using histamine iontophoresis) and pain (using topical mustard oil) in healthy human volunteers, measured using visual analogue scale (VAS) ratings. The effects of the following counterstimuli were evaluated: innocuous vibration; innocuous transcutaneous electrical nerve stimulation (TENS); innocuous warming of skin; noxious heating of skin; noxious chemical skin stimulation (using mustard oil); mildly noxious constant current transdermal electrical stimulation. Innocuous stimuli applied 2 min after histamine or mustard oil challenge produced a modest reduction of itch and pain ratings (20-30%), which did not persist for more than 20 sec when the counterstimuli were removed. ⋯ The differential effects of noxious counterstimuli on itch and pain do not support the suggestion that itch is a subliminal form of pain. Noxious counterstimuli are likely to act via a central rather than peripheral mechanism. The novel finding that a persistent anti-pruritic state can be induced by transdermal constant current may be useful in conditions of clinical itch.
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This study was conducted to determine the contribution of peripheral inputs from injured and intact afferent fibers to behavioral signs of neuropathic pain, using a previously developed neuropathic rat model. Neuropathic injury was produced by tightly ligating the left L5 and L6 spinal nerves; this procedure induced rats to display neuropathic pain behaviors in the ipsilateral hindlimb. The behaviors included signs of mechanical and cold allodynia, as well as ongoing pain. ⋯ Blocking afferent inputs by application of bupivacaine mimicked the results of dorsal rhizotomy, in a reversible manner. These results suggest that afferent signals from injured and intact fibers play distinctively different roles in neuropathic pain: inputs from injured afferents maintain all components of neuropathic pain, while those from intact afferents mediate evoked pain such as mechanical and cold allodynia. An hypothesis is proposed to explain the results of the present as well as other published studies.
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Comparative Study
Fixed-diameter polyethylene cuffs applied to the rat sciatic nerve induce a painful neuropathy: ultrastructural morphometric analysis of axonal alterations.
Polyethylene cuffs of varying inner diameters were applied to the rat sciatic or sural nerve with the aim of inducing a standardized nerve injury, as assessed by morphometric analyses of fiber-size spectrum alterations, associated with behavioral manifestations of neuropathic pain. The temporal sequence of axonal degeneration and regeneration was examined in parallel with behavioral analyses of pain initiation and recovery over a 6-week postoperative (PO) period. Cuffs of 0.028-0.030" inner diameter loosely enclosed sciatic nerves of young rats and elicited relatively uniform axonal degeneration and 'pain'. ⋯ Consistent behavioral manifestations of pain were achieved over a wide range of fiber spectrum alteration; however, with the largest cuffs or 'bracelets' used in this study, a substantial axonal fiber spectrum change was produced without inducing pain-related behavior, suggesting that decrement in the number of myelinated axons was not always sufficient to elicit pain. Similar morphometric and pathological results were achieved with sural neuropathy after 0.010" ID cuffs and 14 days PO survival. Considering the lack of correlation between axonal alterations and pain, modification in the local intraneurial microenvironment at the site of injury may be a key component of peripheral pain mechanisms; these include changes in the biochemical milieu, increased intraneurial pressure, and altered nociceptor sensitivity or impulse propagation in the relatively intact unmyelinated axon population.