Naunyn-Schmiedeberg's archives of pharmacology
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Naunyn Schmiedebergs Arch. Pharmacol. · Oct 2009
The effects of the TRPV1 receptor antagonist SB-705498 on trigeminovascular sensitisation and neurotransmission.
This report examines the effect of the transient receptor potential vanilloid 1 receptor antagonist SB-705498 on neurotransmission and inflammation-induced sensitisation in the trigeminovascular sensory system. A single-neuron electrophysiological animal model for neurovascular head pain was used to evaluate dural and facial noxious inputs and the effects of SB-705498 administered by intravenous (i.v.) injection. Electrical and mechanical stimulation of the dura mater and the facial skin activated second-order neurons in the trigeminal nucleus caudalis of cats, with A-delta latencies. ⋯ Significant brain levels of SB-705498 were maintained for up to 9 h. These results suggest that SB-705498 may be an effective suppressant and reversal agent of the sensitisation to sensory input which follows inflammation in the trigeminovascular sensory distribution but may not be particularly useful in blocking primary pain processes such as migraine headache. SB-705498 could thus potentially prevent, modify or reverse the cutaneous trigeminal allodynia seen in certain migraine conditions, especially "transformed" migraine.
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Naunyn Schmiedebergs Arch. Pharmacol. · Oct 2009
The peripheral administration of a nitric oxide donor potentiates the local antinociceptive effects of a DOR agonist during chronic inflammatory pain in mice.
Several works reveal that nitric oxide could enhance the peripheral antinociception induced by opioids during acute inflammation. Nonetheless, the role of nitric oxide in the local antinociceptive effects of delta-opioid receptor (DOR) agonists during chronic peripheral inflammation is not known. The aim of this study is to evaluate whether nitric oxide would enhance the local antinociceptive effects of a DOR agonist during chronic inflammatory pain in mice. ⋯ Moreover, the co-administration of NOC-18 with DPDPE significantly increased the antinociceptive effects produced by DPDPE from 1 to 10 days of CFA-induced inflammatory pain (P < 0.05). These effects were completely blocked by naltrindole and naloxone methiodide. Our results demonstrate that nitric oxide might enhance the local antinociceptive effects of a DOR agonist during chronic inflammatory pain by interaction with peripheral DOR, representing a useful strategy for an efficient antinociceptive treatment of peripheral inflammatory pain.