Pain
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The anticonvulsant gabapentin is effective against neuropathic pain, but the primary site(s) and mechanism(s) of action are unknown. In order to explore the relative contribution of spinal versus supra-spinal mechanisms to the antinociceptive effect of gabapentin, this study used two differentially integrated nociceptive tests. We systematically compared the effects of various doses of gabapentin on the paw withdrawal to pressure (PWTP), a spinally coordinated reflex and the vocalization threshold to paw pressure (VTPP), a supra-spinal integrated test in the sciatic nerve constriction rat model of neuropathic pain. ⋯ Gabapentin at 100 mg/kg but not at 30 mg/kg produced motor deficits in animals using the rotarod test. Taken together, our findings suggest that low doses of gabapentin have a preferential action on the more integrated pain-related behaviour in neuropathic rats. The present results confirm that gabapentin may be a useful approach for the clinical management of several aspects of neuropathic pain.
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Studies have shown that the steroid anaesthetic alphaxalone positively modulates gamma-aminobutyric acid (GABA) receptors in vitro. It has also been reported that positive modulation of GABA(A) receptors in the rat spinal cord can produce antinociception in vivo. This present study looks at the interaction of an intraperitoneal injection (i.p.) of the steroid anaesthetic combination Saffan (alphaxalone 9 mg/ml, alphadolone acetate 3 mg/ml) with GABA(A) receptors in the spinal cord. ⋯ Alphadolone caused no sedation but it did cause antinociceptive effects equal in magnitude to those produced by Saffan. We conclude that Saffan produces antinociception in rats when given i.p. by an interaction with spinal GABA(A) receptors. Furthermore, this antinociception is due to the alphadolone content of the neurosteroid anaesthetic and not the alphaxalone.
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Ovariohysterectomy in the rat led to the induction of abdominal postures and referred mechanical allodynia in the hind paws. The latter was differentiated into static and dynamic subtypes. The abdominal postures were present up to 4-5 h, whilst the two types of allodynia lasted for at least 2 days. ⋯ In contrast, administration of three doses of morphine (3 mg/kg) in a similar dosing regime but starting 24 h after surgery, only blocked the two types of allodynia for 4 h. These data indicate the importance of blocking the induction phase of surgical pain and support the concept of pre-emptive analgesia. It is suggested that the ovariohysterectomy model should prove to be useful for studying mechanisms and designing novel therapeutic strategies for the treatment of post-operative pain.
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Randomized Controlled Trial Clinical Trial
Intravenous morphine in postoperative infants: intermittent bolus dosing versus targeted continuous infusions.
Eighty-three infants received i.v. morphine following surgery as a continuous infusion to a targeted morphine concentration of 20 ng ml(-1) (n = 56) or as intermittent bolus doses as needed (n = 27). Ventilation was compared in the two groups by continuous pulse oximetry, by venous blood gases on postoperative day 1 (POD 1) and by CO2 response curves. Infant pain scores were done to assess analgesia every 4 h. ⋯ Morphine clearance increased with age. Infants with detectable morphine also had measurable morphine-6-glucuronide in both groups. Oral intake began at 16 h in both groups and other side effects were infrequent.
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To investigate the influence of chronic nociceptive pain on endogenous pain modulation, the effect of heterotopic noxious conditioning stimulation (HNCS) on perception of various somatosensory modalities was assessed in 15 patients with painful osteoarthritis of the hip. Thirteen patients were re-assessed when pain-free 6-14 months following surgery. Sex- and age matched healthy subjects assessed at similar time intervals served as controls. ⋯ In the second session, pressure pain thresholds increased during the tourniquet test in controls (P < 0.001) and in patients (P < 0.02). In conclusion, no pressure pain modulation was induced by HNCS in patients before surgery, as opposed to controls, suggesting a dysfunction in systems subserving 'diffuse noxious inhibitory controls' (DNIC). Normal pressure pain modulation induced by HNCS was seen when patients were re-assessed in a pain-free state following surgery, indicating that the dysfunction of DNIC had been maintained by chronic nociceptive pain.