Pain
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Supraspinal opioid analgesia is mediated in part by connections between the periaqueductal gray (PAG) and rostral ventromedial medulla (RVM). Morphine analgesia elicited from the PAG is respectively decreased by selective serotonergic and opioid receptor antagonists administered into the RVM, and increased by RVM neurotensin antagonists. Since glutamate and excitatory amino acid (EAA) receptors are also active in the RVM, the present study evaluated whether either competitive (AP7) or non-competitive (MK-801) N-methyl-D-aspartate (NMDA) antagonists or a kainate/AMPA (CNQX) antagonist microinjected into the RVM altered morphine (2.5 micrograms) analgesia elicited from the PAG as measured by the tail-flick and jump tests. ⋯ In contrast, small but significant reductions in mesencephalic morphine analgesia occurred on the jump test following CNQX (0.5 microgram, 2.2 nmol) in the RVM. NMDA antagonists did not markedly alter either basal nociceptive thresholds following RVM administration, or mesencephalic morphine analgesia following administration into medullary placements lateral or dorsal to the RVM. These data implicate EAA and particularly NMDA receptors in the RVM in modulating the transmission of opioid pain-inhibitory signals from the PAG.
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In this study, we developed a rat model of incisional pain. A 1-cm longitudinal incision was made through skin, fascia and muscle of the plantar aspect of the hindpaw in halothane-anesthetized rats. Withdrawal responses were measured using von Frey filaments at different areas around the wound before surgery and for the next 6 days. ⋯ Even remote sites as much as 10 mm from the wound showed persistent mechanical hyperalgesia. Selective denervations of the rat hindpaw prior to foot incision revealed both the sural and tibial nerves were responsible for transmitting input from the incision that produces hyperalgesia. This model should allow us to understand mechanisms of sensitization caused by surgery and investigate new therapies for postoperative pain in humans.
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Randomized Controlled Trial Comparative Study Clinical Trial Controlled Clinical Trial
NMDA receptor blockade in chronic neuropathic pain: a comparison of ketamine and magnesium chloride.
Ten patients (4 female, 6 male) aged 34-67 years suffering from peripheral neuropathic pain participated in a double-blind placebo-controlled study where ketamine or magnesium chloride were administered by a 10 min bolus infusion (ketamine: 0.84 mumol/kg = 0.2 mg/kg, magnesium: 0.16 mmol/kg) followed by a continuous infusion (ketamine: 1.3 mumol/kg/h = 0.3 mg/kg/h, magnesium: 0.16 mmol/kg/h). Ongoing pain determined by VAS score, area of touch-evoked allodynia, detection and pain thresholds to mechanical and thermal stimuli were measured before and during drug infusion. Ketamine produced a significant reduction of spontaneous pain (57%) and of the area of allodynia (33%). ⋯ Following ketamine there was a significant correlation between the reduction in ongoing pain and reduction in area of touch-evoked allodynia. Detection and pain thresholds to mechanical and thermal stimuli were not significantly changed by the drugs. These findings suggest that both ongoing pain and touch-evoked pain (allodynia) in neuropathic pain are inter-related phenomena, which may be mediated by the same mechanism and involving a N-methyl-D-aspartate receptor.
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Randomized Controlled Trial Comparative Study Clinical Trial
Amitriptyline effectively relieves neuropathic pain following treatment of breast cancer.
The effectiveness of amitriptyline in relieving neuropathic pain following treatment of breast cancer was studied in 15 patients in a randomised, double-blind placebo-controlled crossover study. The dose was escalated from 25 mg to 100 mg per day in 4 weeks. The placebo and amitriptyline phases were separated by a 2-week wash-out period. ⋯ The 'poor responders' reported significantly more adverse effects with amitriptyline and placebo than the good responders. It is concluded that amitriptyline effectively reduced neuropathic pain following treatment of breast cancer. However, the adverse effects of amitriptyline put most of the patients off from using the drug regularly.
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Randomized Controlled Trial Clinical Trial
Cognitive coping and appraisal processes in the treatment of chronic headaches.
The purpose of the present study was to investigate the active cognitive ingredients of change in psychological treatments for long-term chronic headache complaints. The primary questions this study addressed were: (1) Is a cognitive self-hypnosis training which explicitly attempts to change appraisal and cognitive coping processes more effective in producing these changes than a relaxation procedure, and (2) are changes in pain appraisal and cognitive coping related to changes in pain and adjustment in the short and long term? A total of 144 patients were assigned at random to a cognitive self-hypnosis (CSH) treatment or autogenic training (AT) with a duration of 7 weeks. ⋯ Cognitive therapy was more effective than relaxation training in changing the use of cognitive coping strategies which were the direct targets of treatment. However, treatment effects were only related with changes in the use of coping strategies and appraisal processes to a limited extent and the mediational role of cognitive processes in pain reduction and better adjustment was inconclusive.