Phenotype and Function of Somatic Primary Afferent Nociceptive Neurones with C‐, Aδ‐ or Aα/β‐Fibres

Abstract

Primary afferent neurones convey to the central nervous system information about the external and internal environments. They include low threshold neurones that respond to non-damaging, low intensity, stimuli and normally give rise to sensations other than pain, and high threshold or nociceptive neurones that respond to high intensity, potentially damaging stimuli and often result in a sensation of pain. This review will focus on somatic nociceptive afferent neurones, that is, those that project to the body wall (skin and muscle).Somatic nociceptive afferent neurones may be primarily exteroceptive or interoceptive. Exteroceptive nociceptive afferent neurones detect external noxious stimuli and provide the information necessary for withdrawal from that stimulus, while interoceptive nociceptive neurones detect noxious stimuli of internal origin, including changes that threaten homeostasis and/or result from damage to the tissues. Logically since the stimulus originates within the tissue, withdrawal makes no sense. However, the influence of interoceptive nociceptors on cardiovascular and other homeostatic control centres, does make sense.Both interoceptive and exteroceptive nociceptive afferent neurones are therefore important for the maintenance of internal homeostasis. There are, in addition, efferent effects of certain peptide-expressing primary afferent nociceptive neurones. In response to noxious stimuli these release peptides (substance P and/or calcitonin gene-related peptide (CGRP)) peripherally which have vasoactive effects, promoting inflammatory responses and thus healing of the tissues (Brain & Williams, 1985, 1988. These neurones are therefore thought to be important in the maintenance of tissue integrity, an important aspect of homeostasis. However, nociceptive neurones are more commonly considered in the context of the generation of pain sensation than in the context of their homeostatic function, perhaps because the unpleasant conscious sensation of pain demands our attention above other considerations.While discussing the homeostatic role of somatic primary afferent neurones, it may be useful to consider which types of unit may contribute more to exteroception and which to interoception. To some extent this is an unreal distinction, as the peripheral terminals of sensory nerve cells are

Opposing effects of spinal nerve ligation on calcium-activated potassium currents in axotomized and adjacent mammalian primary afferent neurons

“…With regard to these I K(Ca) blockers, apamin is a selective blocker of SK channels with IC 50 63 pM for the SK2, 2 nM for the SK3 subtype, and a range between 3.3 and 12 nM for SK1 [78]. Iberiotoxin selectively blocks BK channels with IC 50 in the low nM range [54], and clotrimazole blocks IK channels with IC 50 50 nM [22].…”

“…4-AP blocks delayed rectifier and A-type potassium channels [32] (IC 50 1-2 mM for various neuronal K+ channels [18,79,84]), glibenclamide selectively blocks ATP-sensitive K + channels [32] (IC 50 for inhibition of levcromakalim-activated current in adult rat intracardiac ganglionic neurons 55 nM [35]), and TEA blocks delayed rectifier, inward rectifier, A-type, BK and ATP-sensitive K + channels [32] (IC 50 in the low mM range for voltage-gated K+ currents in neurons [49], or in the 1-100 mM range for blocking various neuronal K + channels [41,67]). …”

“…These correspond to somata of C, Aδ and Aβ nerve fibers, respectively, that mediate different physiological functions. Medium sized somata correspond to Aδ fibers, that contain a heterogeneous population of neurons containing nociceptors and non-nociceptors (low threshold mechanoreceptors) [50]. We therefore chose to focus on this representative population.…”

Nociceptors: the sensors of the pain pathway

“…Labeling with retrograde dyes injected into the target tissue has enabled characterization of functional attributes of the soma of nociceptors innervating those tissues. The heterogeneity of functional phenotypes observed in isolated sensory cell bodies (46,47) appears to reflect the variability observed in cutaneous nociceptor fiber types observed in studies in which recordings from fiber or soma during receptive field stimulation are combined with subsequent nociceptor labeling to identify terminal morphology (48,49) and the expression of nocisensors (50), markers, and peptides (48) ( Table 1). Nociceptors differentially express a variety of anatomical and biochemical markers (e.g., the expression of versican, the binding partner for the isolectin B4 [IB4]; ref.…”

Morphological and functional diversity of first-order somatosensory neurons

“…Many studies have addressed the question of correlations of action potential shape with sensory receptor functions (reviewed by Scott 1992;Lawson 2002). Although it has been suggested that differences in AP shape correlates with conduction velocity, evidence suggests a more important correlation with sensory function.…”