Sensory input to the central nervous system from the lungs and airways: A prominent role for purinergic signalling via P2X2/3 receptors

Specific subpopulations of lung-related primary afferent neurons in dorsal root and vagal sensory ganglia have been reported to express P2X2 and P2X3 receptors both in the neuronal cell bodies and in their peripheral terminals. The afferent innervation of airways and lungs is organised as sensory receptor structures, of which at least seven types with a vagal origin and two with a spinal origin have been reported. In view of the recently suggested therapeutic promise of ATP antagonism - specifically at P2X3 receptor expressing nociceptive fibres - in respiratory disorders, the present work focusses on four distinct populations of pulmonary sensory receptors that have so far been reported to express P2X2/3 receptors. Three of them originate from myelinated nerve fibres that display similar mechanosensor-like morphological and neurochemical characteristics. Two of the latter concern vagal nodose sensory fibres, either related to pulmonary neuroepithelial bodies (NEBs), or giving rise to smooth muscle-associated airway receptors (SMARs); the third gives rise to visceral pleura receptors (VPRs) and most likely arises from dorsal root ganglia. The fourth population concerns C-fibre receptors (CFRs) that also derive from neuronal cell bodies located in vagal nodose ganglia. Although the majority of the airway- and lung-related sensory receptors that express P2X2/3 receptors apparently do not belong to accepted nociceptive populations, these data definitely point out that ATP may be an important player in the physiological transduction of different lung-related afferent signals from the periphery to the CNS. The observed variety within the populations of pulmonary sensory receptors that express P2X2/3 receptors argues for a critical and careful interpretation of the functional data.