Primary afferent neurons

This is an unconventional reflex mediated by capsaicin-sensitive primary afferent neurons. In fact, an adequate stimulus can directly excite a peripheral terminal... 

Diuretics This indicates the unique property of capsaicin-sensitive primary afferent neurons to release mediators (neuropeptides and others) from both peripheral and central nervous system terminals upon adequate stimulation. Capsaicin and other chemical (protons) or physical (heat) stimuli release mediators from both peripheral and... 

GABAergic presynaptic inhibition of excitatory transmission of primary afferent neurones of the spinal cord resulting in epileptiform convulsions, myosis, and dyspnea with more or less prolonged apnea. 

A highly simplified diagram of the intestinal wall and some of the circuitry of the enteric nervous system (ENS). The ENS receives input from both the sympathetic and the parasympathetic systems and sends afferent impulses to sympathetic ganglia and to the central nervous system. Many transmitter or neuromodulator substances have been identified in the ENS see Table 6-1. ACh, acetylcholine AC, absorptive cell CM, circular muscle layer EC, enterochromaffin cell EN, excitatory neuron EPAN, extrinsic primary afferent neuron 5HT, serotonin IN, inhibitory neuron IPAN, intrinsic primary afferent neuron LM, longitudinal muscle layer MP, myenteric plexus NE, norepinephrine NP, neuropeptides SC, secretory cell SMP, submucosal plexus. 

Schematic diagram of a primary afferent neuron mediating pain, its synapse with a secondary afferent in the spinal cord, and the targets for local pain control. The primary afferent neuron cell body is not shown. At least three nociceptors are recognized acid, injury, and heat receptors. The nerve ending also bears opioid receptors, which can inhibit action potential generation. The axon bears sodium channels and potassium channels (not shown), which are essential for action potential propagation. Synaptic transmission involves release of substance P, a neuropeptide (NP) and glutamate and activation of their receptors on the secondary neuron. Alpha2 adrenoceptors and opioid receptors modulate the transmission process.

Following inflammation there is a 10-fold increase in axons expressing AMPA or kainate receptors (Coggeshall and Carlton, 1999). In anaesthetized rats, antagonism of AMPA/kainate receptors inhibits dorsal horn neuronal responses induced by innocuous and noxious mechanical stimulation of a chronically inflamed ankle (Neugebauer et al., 1994). Application of kainate to the rat hindpaw induces activation of primary afferent neurons, an effect that is reduced by the AMPA/kainate antagonist DNQX (Ault and Hildebrand, 1993). 

The central release of ATP from dorsal horn synaptosomes was proven by White et al. (1985). Further studies (Sawynok et al., 1993) suggest that ATP can be released from central terminals of primary afferent neurons as well as from terminals of non-primary afferents within the dorsal horn and that ATP and GABA are cotransmitters at many synapses in the dorsal horn (Jo and Schlichter, 1999). After being released ATP acts on specific receptors, designated as P2 purinoreceptors, on the cell surface. 

In behavioral tests, the actions of peripherally-administered ATP are pro-nociceptive. These nociceptive responses have been suggested to be due to direct activation of peripheral nerve terminals (Hies and Norenberg, 1993). ATP produces depolarization when applied to the cell bodies of primary afferent neurons located within the dorsal root ganglia (DRG) (Jahr and Jessell, 1983). The depolarizing effect of ATP results from the activation of a non-selective cation channel (Bean, 1990) and is blocked by P2 purinoreceptor antagonists (Tsuda et al., 1999), indicating that excitation is mediated via ionotropic P2X purinoreceptors. 

Weihe, E. Neuropeptides in primary afferent neurons. In Primary afferent neurons, 1990, edited by W. Zenker, and W. Neuhuber, 127-159, Plenum Press, New York. 

Capsicum, also known as chili or paprika, is the fruit of various Capsicum species. It is widely used as a spice and, traditionally, it has been used internally for colic, flatulent dyspepsia, chronic laryngitis, insufficiency of peripheral circulation, and externally for neuralgia. Capsaicin (the active pungent ingredient) has been used extensively as a probe to elucidate the function of sensory neurons in various organs and systems (including the stomach), because of its ability to excite and later defunctionalize a subset of primary afferent neurons. 

Ingram SL, Williams JT (1996) Modulation of the hyperpolarization-activated current (Ih) by cyclic nucleotides in guinea-pig primary afferent neurons. J Physiol 492 ( Pt 1) 97 106 Ito M (2001) Cerebellar long-term depressionxharacterization, signal transduction, and functional roles. Physiol Rev 81 1143-95... 

It is well known that signal transduction of pain initiates in primary afferent neurons and transmits to the dorsal horn of the spinal cord (Scholz and Woolf, 2002). Signal transduction in the spinal cord is important for nociception, but dynamic change (i.e., central sensitization) and neuronal plasticity associated with glial activation also have important roles in neuropathic pain (Inoue et al., 2007 Tsuda et al., 2005). Central sensitization was demonstrated in neuropathic pain... 

Wiley, J. W., Moises, H. C., Gross, R. A., and MacDonald, R. L. (1997). Dynorphin A-mediated reduction in multiple calcium currents involves a G (o) alpha-subtype G protein in rat primary afferent neurons. J. Neurophysiol. 77, 1338—1348. 

Rashid, M., Inoue, M., Bakoshi, S. and Ueda, H. (2003) Increased expression of vanilloid receptor 1 on myelinated primary afferent neurons contributes to the antihyperalgesic effect of capsaicin cream in diabetic neuropathic pain in mice. Journal of Pharmacology And Experimental Therapeutics DOI 10.1124/jpet.103.050948. 

Habler et al. (1990, 1992) examined the functional properties of unmyelinated and myelinated primary afferent neurons innervating the pelvic viscera in anesthetized cats. The axons were isolated from the intact dorsal root and the intact or chronically de-efferented ventral root of segment S2. The responses of the neurons were studied with natural stimulation of the urinary bladder using innocuous or noxious increases of intravesical pressure. 

Maggi CA, Giuliani S (1992) Non-adrenergic, non-cholinergic excitatory innervation of the guinea pig renal pelvis Involvement of capsaicin-sensitive primary afferent neurons. J Urol 147 1394-1398... 

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