[What is a nociceptor?].

INTRODUCTION

Nociceptors can be defined as sensory receptors that are activated by noxious stimuli that damage or threaten the body's integrity. Nociceptors belong to the slowly conducting afferent A delta and C fibres. They are classified according to their responses to mechanical, thermal, and chemical stimuli.

SKIN NOCICEPTORS

In the skin, high-threshold mechano-nociceptors (HTMs) and mechano-heat nociceptors of A and C fibres (AMHs and CMHs) are frequently found. CMHs are usually called polymodal C fibres (CPMs) if they also show chemosensitive properties. Sensations of sharp pain are evoked by intraneural microstimulation of nociceptive A delta fibres, whereas stimulation of C fibres causes dull pain sensations. NOCICEPTORS OF DEEP TISSUES AND VISCERA: Slowly conducting afferents of deep tissues (muscles, joints) are primarily classified according to their mechanosensitivity. High-threshold afferents in somatic and visceral tissues are specifically activated by noxious mechanical stimuli. Many visceral afferents, however, are already activated by peristaltic contractions encoding the stimulus intensity over a wide range. High proportions of somatic and visceral nociceptors can be excited or sensitised by various irritants and inflammatory mediators such as capsaicin, bradykinin, prostaglandins, leukotrienes, serotonin, histamine, and free radicals. As a special class of nociceptors, mechano-insensitive or "silent" afferents have been found in nearly all tissues. Silent afferents become mechanosensitive only after long noxious stimulation, e.g., during an inflammation.

FREE NERVE ENDINGS

"Free nerve endings", which are regarded as the morphological correlatives of nociceptors, usually consist of bundles of unmyelinated fibres. With electron microscopy varicose segments of the sensory axon are visible that are characterised by free areas of axolemma, accumulations of mitochondria and vesicles, and a modified axoplasm. These presumptive receptive sites are periodically arranged along the whole course of the sensory endings at a length of up to several hundred microns. Additionally, the fine sensory endings are branched, forming tree-like structures, and frequently innervate different types of tissues. Studies correlating structure and function of articular afferents provide evidence for a close relationship between topographical and functional properties of sensory endings. High-threshold afferents (nociceptors) seem to terminate in structures of dense connective tissue. Proportions of nociceptors contain neuropeptides such as substance P and calcitonin gene-related peptide, which are released from the activated nociceptive terminals and cause neurogenic inflammation, including precapillary vasodilatation and postcapillary plasma extravasation.

PAIN TREATMENT

Experimental and clinical progress has been achieved in using the nociceptor as a target for chemical anti-nociception and treatment of pain. Substances that act directly or indirectly on the nociceptor are steroidal and non-steroidal analgesics, capsaicin analogs, bradykinin antagonists, opioids, and (in the trigeminal system) 5-hydroxytryptamine agonists.