Chemosensory properties of the trigeminal system

Abstract

The capacity of cutaneous, including trigeminal endings, to detect chemicals is known as chemesthesis or cutaneous chemosensation. This sensory function involves the activation of nociceptor and thermoreceptor endings and has a protective or defensive function, as many of these substances are irritants or poisonous. However, humans have also developed a liking for the distinct sharpness or pungency of many foods, beverages, and spices following activation of the same sensory afferents. Our understanding of the cellular and molecular mechanisms of chemosensation in the trigeminal system has experienced enormous progress in the past decade, following the cloning and functional characterization of several ion channels activated by physical and chemical stimuli. This brief review attempts to summarize our current knowledge in this field, including a functional description of various sensory channels, especially TRP channels, involved in trigeminal chemosensitivy. Finally, some of these new findings are discussed in the context of the pathophysiology of trigeminal chemosensation, including pain, pruritus, migraine, cough, airway inflammation, and ophthalmic diseases.

Keywords: Chemestesis; KCNK; TRP channel; TRPA1; TRPM8; TRPV1; TRPV2; TRPV3; asthma; capsaicin; cough; dry eye; menthol; pain; pungency; spices.

Figure 1

Molecular determinants of chemosensation in trigeminal nerve terminals. Branches of the human trigeminal nerve innervating the face, the eye, and the nasal and oral cavities. Temperature and many chemical agents can stimulate chemosensitive channels directly. These channels are expressed in sensory nerve terminals and mucosal epithelial cells or skin keratinocytes. The opening of cationic channels (TRPs, ASICs) or the closing of potassium-selective channels (KCNK) generate a graded transduction current, depolarization, and the firing of action potentials. Voltage gated sodium (Na_V), calcium (Ca_V), and potassium (K_V) channels participate in action potential electrogenesis and propagation of the nerve impulse to the brainstem. Mechanical deformation of the skin can trigger the release of ATP from keratinocytes and the activation of purinergic (P2_X) receptors from sensory nerve terminals.

Figure 2

Chemosensitive responses of cultured mice trigeminal sensory neurons. Fura-2 calcium imaging of agonist-evoked responses of individual sensory neurons to capsaicin (100 nM) and warm temperature (A), menthol (100 μM) and cold temperature (B), nifedipine (10 μM) and mustard oil (100 μM) (C), clotrimazole (10 μM), capsaicin (100 μM), menthol (100 μM), and mustard oil (100 μM) (D), nicotine (1 mM) and mustard oil (100 μM) (E), ATP (1 mM) (F). Responses were obtained with different imaging systems, and absolute amplitude cannot be compared. (A) by R. Madrid (unpublished), (B) from Madrid et al. (159), (C) from Fajardo et al. (113), (D) from Meseguer et al. (160), (E) by V. Meseguer (unpublished), and (F) by E. de la Pena (unpublished). The record in (D) was obtained from a Trpv1^−/− mouse.