Articles: hyperalgesia.
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Clin. Exp. Pharmacol. Physiol. · Nov 2006
Effects of trolox on nerve dysfunction, thermal hyperalgesia and oxidative stress in experimental diabetic neuropathy.
1. Diabetic neuropathy is one of the most common complications of diabetes and oxidative stress has been implicated to play a major role in its pathophysiology. 2. In the present study, we targeted oxidative stress using trolox, an anti-oxidant, in streptozotocin-induced diabetic neuropathy in rats. 3. ⋯ Two weeks treatment with trolox (10 and 30 mg/kg, i.p.) started on completion of the 6th week of diabetes significantly improved MNCV, NBF and inhibited thermal hyperalgesia. Trolox treatment also improved the activity of anti-oxidant enzymes and inhibited lipid peroxidation in sciatic nerves of diabetic rats. 6. The results of the present study suggest the beneficial effects of trolox in experimental diabetic neuropathy.
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Neurobiology of disease · Nov 2006
Mechanical hyperalgesia correlates with insulin deficiency in normoglycemic streptozotocin-treated rats.
The triggers and pathogenesis of peripheral diabetic neuropathy are poorly understood, and this study evaluated the role of insulinopenia in nociceptive abnormalities in the streptozotocin (STZ) rat model of diabetes to test the hypothesis that, in addition to hyperglycemia, impairment of insulin signaling may be involved in progression of neuropathy. We measured blood glucose, plasma insulin, and sciatic nerve glucose and sorbitol levels, and withdrawal thresholds for hind limb pressure pain and heat pain in STZ-injected rats that developed hyperglycemia or remained normoglycemic. ⋯ These pain thresholds did not correlate with blood or nerve glucose or sorbitol levels, but both correlated with plasma insulin level in STZ-normoglycemic rats, and low-dose insulin replacement normalized the pressure threshold without affecting blood glucose level. Thus, at least one of early signs of diabetic neuropathy in STZ-treated rats, mechanical hyperalgesia, can be triggered by moderate insulinopenia, irrespective of glycemic status of the animals.
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Comparative Study
Robust increase of cutaneous sensitivity, cytokine production and sympathetic sprouting in rats with localized inflammatory irritation of the spinal ganglia.
We investigated the role and mechanisms of inflammatory responses within the dorsal root ganglion (DRG) in the development of chemogenic pathological pain. DRG inflammation was induced by a single deposit of the immune activator zymosan in incomplete Freund's adjuvant in the epidural space near the L5 DRG via a small hole drilled through the transverse process. After a single zymosan injection, rats developed bilateral mechanical hyperalgesia and allodynia which began by day 1 after surgery, peaked at days 3-7, and lasted up to 28 days. ⋯ Changes in cytokines and spontaneous activity correlated with the time course of pain behaviors, especially light stroke-evoked tactile allodynia. Finally, local inflammation induced extensive sprouting of sympathetic fibers, extending from vascular processes within the inflamed DRG. These results demonstrate the feasibility of inducing chronic localized inflammatory responses in the DRG in the absence of traumatic nerve damage, and highlight the possible contribution of several inflammatory cytokines/chemokines to the generation of spontaneous activity and development and persistence of chemogenic pathologic pain.
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To investigate mechanisms by which diabetes alters sensory processing, we measured levels of amino acid neurotransmitters in spinal dialysates from awake, unrestrained control and diabetic rats under resting conditions and following hind paw formalin injection. Under resting conditions, glutamate concentrations in spinal dialysates were significantly (P<0.05) decreased in diabetic rats compared to those of control rats whereas aspartate, taurine, glycine and citrulline remained unchanged and GABA was significantly (P<0.05) increased. Noxious stimulation of the hind paw by subcutaneous injection of 0.5% formalin into the dorsum caused a defined flinching behavior in the afflicted paw, and the amount of flinching was significantly (P<0.05) greater in diabetic rats than in controls. ⋯ Formalin injection did not alter dialysate GABA concentrations in control rats, whereas in diabetic rats there was an increase of 151+/-15% above basal levels. These findings indicate that the selective depression of basal and stimulus-evoked glutamate levels in the spinal cord of diabetic rats occurs in parallel with elevated spinal GABA levels. Because increased pain-associated behavior is accompanied by an attenuated spinal glutamate spike following paw formalin injection, hyperalgesia in diabetic rats does not appear to be secondary to enhanced glutamatergic input to the spinal cord.