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    Combined systemic administration of morphine and magnesium sulfate attenuates pain-related behavior in mononeuropathic rats
    (Elsevier Science Bv, 2002) Ulugol, A; Aslantas, A; Ipci, Y; Tuncer, A; Karadag, CH; Dokmeci, I
    The response to opioids is reduced in neuropathic pain states. We examined the effect of the combination of morphine (0.1 mg/kg) and magnesium sulfate (125 mg/kg) on behavioral signs of neuropathic pain in spinal nerve ligated rats. Administered alone, neither drug produced any effect, but the combination exerted a significant anti-allodynic effect, which was partially reversed by naloxone. These results suggest that combining low doses of magnesium sulfate with opiates might be an alternative in treating neuropathic pain, with reduced risk of side effects. (C) 2002 Elsevier Science B.V. All rights reserved.
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    The effect of combined systemic administration of morphine and L-name, a nitric oxide synthase inhibitor, on behavioral signs of neuropathic pain in rats
    (John Wiley & Sons Ltd, 2002) Ulugol, A; Aslantas, A; Karadag, HC; Bulbul, ED; Tuncer, A; Dokmeci, I
    The controversy over using opioids for managing chronic neuropathic pain is widely acknowledged, and nitric oxide (NO) is suggested to play an important role in the maintenance of the behavioral signs of neuropathic pain. We evaluated the effect of combined systemic administration of morphine and N-G-nitro-L-arginine-methyl ester (L-NAME), a NO synthase (NOS) inhibitor, on allodynia in the spinal nerve ligation model of pain in rats. Nerve injury was produced by tight ligation of the left L5 and L6 spinal nerves and this procedure resulted in neuropathic pain behaviors in the ipsilateral hindlimb. Mechanical and cold allodynia were detected, respectively, by application of von Frey filaments or acetone to the plantar surface of the foot. Morphine (0.1-10 mg/kg, i.p.) and L-NAME (3-30 mg/kg, i.p.) reduced mechanical and cold allodynia with their higher doses. Combining subthreshold dose of L-NAME (3 mg/kg, i.p.) with morphine, an appreciable increase in the antiallodynic effect of morphine was observed. This effect was prevented by L-arginine (500 mg/kg, i.p.) and naloxone (I mg/kg, i.p.). These results suggest that combining morphine with a NOS inhibitor may be a promising approach in the treatment of neuropathic pain.
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    Involvement of adenosine in the anti-allodynic effect of amitriptyline in streptozotocin-induced diabetic rats
    (Elsevier Sci Ireland Ltd, 2002) Ulugol, A; Karadag, HC; Tamer, M; Firat, Z; Aslantas, A; Dokmeci, I
    Recent observations suggest the involvement of adenosine in the peripheral antinociceptive effect of amitriptyline in nerve-injury-induced neuropathic pain. The aim of the present investigation was to evaluate, firstly, the peripheral and systemic effects of amitriptyline on tactile allodynia in the streptozotocin (STZ)-induced diabetic rat model of neuropathic pain and, secondly, whether caffeine coadministration affects the actions of amitriptyline. Diabetes was induced by a single intraperitoneal (i.p.) injection of STZ (50 mg/kg), and tactile allodynia was detected by application of von Frey filaments to the ventral surface of the hindpaw. Both systemic (0.5-2.0 mg/kg, i.p.) and peripheral (10-100 nmol, subcutaneously (s.c.)) administration of amitriptyline were found to produce increases in paw withdrawal thresholds, at higher doses. Coadministration of caffeine (5 mg/kg, i.p.; 1500 nmol, s.c.), at doses which produced no effect on its own, partially reversed systemic and local anti-allodynic effects of amitriptyline. These results indicate an anti-allodynic effect of both peripheral and systemic amitriptyline, and suggest the involvement of endogenous adenosine in the action of amitriptyline in this rat model of painful diabetic neuropathy. These data also suggest that topical application of tricyclic antidepressants may be useful in treating neuropathic pain in diabetics. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.