C fibres

C-fibre afferents from the aitways contain peptide tachykinin transmitters such as substance P (SP) and neurokinins A and B (NKA and NKB). Stimulation of these nerves can also cause local release of these mediators at their peripheral terminal, allowing them to enhance the activity of the RARs. SP, NKA and NKB act at the tachykinin receptors (NK4-NK3), and so understandably, antagonists for NK2 in particular appear promising in cough. 

Nociceptin and orphanin are synonyms for the peptide that acts at an opioid-like receptor. Nociceptin may act by inhibiting tachykinin release from sensory C-fibres, and a clinical trial has started to test its effects on cough. 

Sensory nerves are peripheral nerves involved in the detection of exogenous and endogenous stimuli for transmission into the CNS. They can be subdivided into RARs and C-fibres according to their channel characteristics. 

The release of some peptides may differ from that of other transmitters, depending on the firing rate of the neurons. The large vesicles needed to store a peptide may need a greater rate of depolarisation for membrane fusion and release of the contents. In the salivary gland the release of vasoactive intestinal polypeptide requires high-frequency stimulation whereas acetylcholine is released by all stimuli. Due to the complexities and problems of access to CNS synapses it is not known if the same occurs here but there is no reason why this should not. In sensory C-fibres a prolonged stimulus appears to be a prerequisite for the release of substance P. 

The best-understood sites of action of morphine are at spinal and brainstem/ midbrain loci, producing both the wanted and unwanted effects of the opioid. The spinal actions of opioids and their mechanisms of analgesia involve (1) reduced transmitter release from nociceptive C-fibres so that spinal neurons are less excited by incoming painful messages, and (2) postsynaptic inhibitions of neurons conveying information from the spinal cord to the brain. This dual action of opioids can result in a... 

The afferent fibres differ in their conduction velocity and degree of myelination, and can be distinguished by their diameter. The large diameter A S-fibres are myelinated by Schwann cells and hence have a fast conduction velocity. This group of nerve fibres innervates receptors in the dermis and is involved in the transmission of low-threshold, non-noxious information, such as touch. The A5-fibre is less densely myelinated and conveys both non-noxious and noxious sensory information. The unmyelinated C-fibre conveys high-threshold noxious inputs and has the slowest conduction velocity of all three fibre types. 

Extensive studies have investigated the organisation and termination patterns of C-fibres, employing various techniques including Golgi staining, degeneration techniques... 

Bradykinin is another chemical with important peripheral actions but, as yet, cannot be manipulated in any direct way by drugs. It is a product of plasma kininogens that find their way to C-fibre endings following plasma extravasation in response to tissue... 

The cells comprising lamina V are more diverse than those of lamina IV and their dendrites extend vertically toward the superficial layers. Cell bodies in lamina V contribute to three projection pathways, the SCT, PSDC and STT. However, the STT cells appear to be predominant in this lamina. Lamina V plays an important role in nociception since it receives both A - and C-fibre inputs. Some cells in lamina V also respond to cutaneous low- and high-threshold mechanical stimuli and receive nociceptive inputs from the viscerae. Many of these neurons also project onto mononeurons and so act as interneurons in the polysynaptic withdrawal reflex to noxious stimuli. 

The arrival of action potentials in the dorsal horn of the spinal cord, carrying the sensory information either from nociceptors in inflammation or generated both from nociceptors and intrinsically after nerve damage, produces a complex response to pain. Densely packed neurons, containing most of the channels, transmitters and receptors found anywhere in the CNS, are present in the zones where the C-fibres terminate... 

There are important inhibitory systems built into the control of events following C-fibre stimulation. Thus, during peripheral noxious stimulation, spinal mechanism, driven by NMDA-receptor-mediated activity, can become active to damp down further neuronal responses, the purine, adenosine (see Chapter 13), appears to be involved in this type of control and has been reported to be effective in humans with neuropathic pain. It is thought that the depolarisations caused by activation of the NMDA receptor increase the metabolic demand on neurons and so ATP utilisation increases. ATP then is metabolised to adenosene and the purine then acts on its inhibitory Ai receptor in the... 

The opiate receptors in the spinal cord are predominantly of the mu and delta type and are found in the C-fibre terminal zone (the substantia gelatinosa) in the superficial dorsal horn. Considerable numbers of ORL-1 receptors are also found in this area. Up to 75% of the opiate receptors are found presynaptically on the C-fibre terminals and when activated inhibit neurotransmitter release. The opening of potassium channels will reduce calcium flux in the terminal and so there will be a resultant decrease in... 

Complete C-fibre inhibitions can be produced under normal conditions but opiates do not always produce a complete analgesia in some clinical situations, especially when the pain arises from nerve damage. Reasons for this are suspected to be excessive NMDA-mediated activity which is hard to inhibit and the mobilisation of cholecysto-kinin in the spinal cord which can act as a physiological antagonist of opiate actions. The idea that pre-emptive analgesia aids post-operative pain relief by preventing the pain-induced activation of these systems is becoming popular. 

Klainer S.M., Thomas J.R., Francis J.C., Fibre-optical, sensors offer a realistic solution to environmental monitoring needs, Sensors Actuators B 1993 11 81-86. 

The Ap fibres are examples of afferents that stimulate inhibitory interneurones (in the substantia gelatinosa (SG)) and, therefore, prevent nociceptive transmission to the CNS. The C fibres are examples of afferents that inhibit inhibitory interneurones and, therefore, enhance nociceptive transmission. Note that both types of fibre stimulate the second-order neurone (2°) directly but it is the intemeurone that modifies the transmission. 

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