ReviewForty years in capsaicin research for sensory pharmacology and physiology
Introduction
The steeply increasing number of publications on capsaicin exceeding 650–700 papers per year is a clear indication that this spicy pungent agent has become nowadays really a “hot” topic in neuroscience. In striking contrast during my fifteen year long “first capsaicin period” (1962–1976) altogether less than 40 papers were published from non-Hungarian sources and very few of them were related to neurobiology in its broadest sense. There are two reasons why the emerging interest is nowdays so high. First, in drug research capsaicin and its receptor have become generally accepted lead and target molecules, respectively. The promising perspective of this trend is to discover the first analgesic and antiinflammatory drug which acts not on cyclooxygenases or opioid receptors but selectively on nociceptors. The second reason is related to the new horizons of the neurohumoral regulatory role of mediators (neuropeptides) released from capsaicin-sensitive nociceptors. It is somehow rewarding for me that in the late sixties just these two reasons – what I formulated in my thesis, early publications and reviews – inspired me to devote all my scientific efforts with limited facilities to break through several burdens in this pathway (Szolcsányi, 1982, Szolcsányi, 1984a, Szolcsányi, 1984b, Szolcsányi, 1990, Szolcsányi, 1991, Szolcsányi, 1993, Szolcsányi, 1996a, Szolcsányi, 1996b, Szolcsányi, 2002, Szolcsányi et al., 1994, Szolcsányi et al., 2004).
Section snippets
Capsaicin desensitization and neurogenic inflammation
Nicholas (Miklós) Jancsó, my mentor with whom I worked together in Szeged until his demise in 1966, discovered around the late forties as an accidental observation that high doses of capsaicin applied topically or later also systemically to mice, rats or guinea-pigs elicit a novel type of analgesia. The so called capsaicin desensitized animals did not react with protective reflexes and inflammation to noxious chemicals although their responsiveness to physical stimuli remained intact (
Actions of capsaicin on thermoregulation
Systemic application of capsaicin or its pungent congeners elicited a pronounced fall in body temperature and this response was also absent in capsaicin desensitized animals. The hypothermic effect of the agent was due to a coordinated heat loss response accompanied by vasodilatation, salivation, fall in metabolic rate at cool ambient temperature and in cats also by panting. Heat loss responses to heating the preoptic area or to intrahypothalamic microinjection of capsaicin were also diminished
Postulation of a capsaicin receptor on polymodal nociceptors
The uniqueness of these pharmacological effects of capsaicin was challenging for further research, but the mechanism behind the extremely long-term capsaicin-induced blockade of chemonociception against such diverse structures as xylene, formaldehyde, veratridine or mustard oil remained enigmatic and seemed to favour some kind of neurotoxicity. Beyond the selective ultrastructural impairment restricted to one set of neurons mentioned before (Szolcsányi et al., 1975), results of three sets of
Dual sensory-efferent function of capsaicin-sensitive nociceptors
Our proposal of “dual sensory-efferent function” for a nerve ending is against the classical works of Bayliss, Bruce and Thomas Lewis on antidromic vasodilatation and axon reflex flare. According to the views of these pioneers signals from sensors are conducted through axonal arborization to nerve terminals specialized for mediator releasing functions (Szolcsányi, 1984b, Szolcsányi, 1988, Szolcsányi, 1996a, Szolcsányi, 1996b). Taking the advantage of the neuroselective action of capsaicin we
The TRPV1/VR1 capsaicin receptor
From the late eighties conclusive evidence has accumulated for the existence of a capsaicin receptor and a novel capsaicin-gated cation channel was identified in patch clamp studies (Bevan and Szolcsányi, 1990). Thus, strong efforts were made to isolate, identify and clone this membrane protein. Finally, it was succeeded by the group of David Julius in 1997 (Caterina et al., 1997). It was named by the authors both as “capsaicin receptor” or as “vanilloid receptor 1” (VR1) and recently renamed
Sensocrine function of capsaicin-sensitive nociceptors
It was serendipity, an unexpected observation made by my coworker Erika Pintér that in the course of rat experiments for mapping neurogenic inflammation in visceral organs by antidromic stimulation of dorsal roots, the cutaneous blueing response to the first stimulation was obviously more pronounced than the effect evoked by a subsequent stimulation of another pair of dorsal roots (Pintér and Szolcsányi, 1995, Pintér and Szolcsányi, 1996). Thus, the paradigm was changed and only single
Acknowledgements
Supported by the Hungarian Academy of Sciences and by research Grants of NRDP 1A/021/2002, OTKA TS-040753 and T-034911.
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