Akihiro Nakamura (1) and Hirohito Shiomi (2)
(1) Department of Clinical Pharmacy, 2 Department of Pharmacology Faculty
of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Hiroshima
729-0292, Japan
Abstract: Cutaneous nociceptors are peripheral receptive endings
of primary sensory neurons activated by noxious stimuli. Nociceptors detect
and signal the presence of tissue-damaging stimuli or the existence of tissue
damage. In this short review, we will focus on the molecular mechanism of
maintenance, activation, inhibition and sensitization in cutaneous nociceptors.
Neurotrophic factors are essential to the development of nociceptors during
embryogenesis. Recent evidences have indicated that nociceptors in the adult
are maintained by either nerve growth factor (NGF) or glial cell line-derived
neurotrophic factor (GDNF). A selective activator of nociceptors is capsaicin,
natural product of capsicum peppers. Recently, the receptor for capsaicin
(the vanilloid receptor 1: VRI) has been cloned, identified and characterized.
VRI seems to play an important role in the activation and sensitization
of nociceptors. In contrast, peripheral endogenous cannabinoids such as
anandamide are novel candidates for mediators that inhibit the excitation
of nociceptors. Intracellular messengers and the mechanisms of signal transduction
in nociceptors have also been studied. Our recent findings provide evidences
demonstrate that an activation of both cAMP- and cGMP-second messenger systems
is required to induce the sensitization of nociceptors. Such emerging evidences
reviewed here would make a significant contribution to further understanding
of the molecular mechanism of nociceptors.
Keywords: Pain, Capsaicin, Neurotrophic factor, Cannabinoid, Nitric oxide
(NO)