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Abstract: In the present study, whole-cell patch clamp recording technique was used to investigate the action of 5-hydroxytryptamine (5-HT) on the function of native neuronal nicotinic acetylcholine receptors expressed in the rat trigeminal ganglion neurons. Inward currents (I nic) caused by externally-applied nicotine were observed in majority of the examined neurons, which were mediated by α-bungarotoxin-insensitive nicotinic acetylcholine receptors. We found that 5-HT could reversibly inhibit I nic in a concentration-dependent manner, and the inhibition did not involve 5-HT receptors. Other serotonergic agents, such as 2-methyl-5-HT, α-methyl-5-HT, sumatriptan and ICS-205,930, also had similar inhibitory effects on I nic. 5-HT inhibited nicotinic acetylcholine receptors in a non-competitive manner, as 5-HT decreased the maximal current response to nicotine but had no effect on the threshold and EC50. The inhibition of I nic by 5-HT was voltage-dependent and became stronger at hyperpolarized potentials. These results indicated that 5-HT directly inhibited nicotinic acetylcholine receptors in the trigeminal ganglion neurons. As a local modulator of the nicotinic acetylcholine receptor, 5-HT might play a role in the modulation of sensory information. [Copyright &y& Elsevier]

Prokineticin 2 (PK2), a new chemokine, causes mechanical hypersensitivity in the rat hind paw, but little is known about the molecular mechanism. Here, we have found that ionotropic P2X receptor is essential to mechanical allodynia induced by PK2. First, intraplantar injection of high dose (3 or 10 pmol) of PK2 significantly increased paw withdrawal response frequency (%) to innocuous mechanical stimuli (mechanical allodynia). And the mechanical allodynia induced by PK2 was prevented by co-administration of TNP–ATP, a selective P2X receptor antagonist. Second, although low dose (0.3 or 1 pmol) of PK2 itself did not produce an allodynic response, it significantly facilitated the mechanical allodynia evoked by intraplantar injection of α,β-methylene ATP (α,β-meATP). Third, PK2 concentration-dependently potentiated α,β-meATP-activated currents in rat dorsal root ganglion (DRG) neurons. Finally, PK2 receptors and intracellular signal transduction were involved in PK2 potentiation of α,β-meATP-induced mechanical allodynia and α,β-meATP-activated currents, since the potentiation were blocked by PK2 receptor antagonist PKRA and selective PKC inhibitor GF 109203X. These results suggested that PK2 facilitated mechanical allodynia induced by α,β-meATP through a mechanism involved in sensitization of cutaneous P2X receptors expressed by nociceptive nerve endings. [ABSTRACT FROM AUTHOR]

Abstract: Acid-sensing ion channels (ASICs), a family of proton-gated cation channels, are believed to mediate pain caused by extracellular acidification. Gastrodin is a main bioactive constituent of the traditional herbal Gastrodia elata Blume, which has been widely used in Oriental countries for centuries. As an analgesic, gastrodin has been used clinically to treat pain such as migraine and headache. However, the mechanisms underlying analgesic action of gastrodin are still poorly understood. Here, we have found that gastrodin inhibited the activity of native ASICs in rat dorsal root ganglion (DRG) neurons. Gastrodin dose-dependently inhibited proton-gated currents mediated by ASICs. Gastrodin shifted the proton concentration–response curve downwards, with a decrease of 36.92±6.23% in the maximum current response but with no significant change in the pH0.5 value. Moreover, gastrodin altered acid-evoked membrane excitability of rat DRG neurons and caused a significant decrease in the amplitude of the depolarization and the number of action potentials induced by acid stimuli. Finally, peripheral applied gastrodin relieved pain evoked by intraplantar injection of acetic acid in rats. Our results indicate that gastrodin can inhibit the activity of ASICs in the primary sensory neurons, which provided a novel mechanism underlying analgesic action of gastrodin. [Copyright &y& Elsevier]