Unmyelinated axons occur in almost all tissues, and the sensory ones generally mediate the senses of pain and temperature. The sensory receptors that respond to injurious stimuli are called nociceptors.
Nociception involves two groups of afferent fibres:
- A-delta fibres which cause a pricking pain (fast pain)
- C-fibres which cause an intense aching pain that is emotionally draining (slow pain).
These terms ‘slow’ and ‘fast’ point to the speed of conduction of these two fibre groups, and the time take for impulses to travel into the CNS.
Both induce flexor and autonomic reflexes.
Nociceptors respond to injurious stimuli caused by
- Intense forces and pressures
- High temperatures (<45 degrees C)
- Strong chemical solutions
- the presence of algesic agents such as bradykinin and sone prostaglandins
The mechanism by which nociceptors respond to these intense stimuli requires membrane proteins called TRPV receptors that excite action potentials in the axons by allowing non-specific ion currents to depolarise the free nerve endings..
Transient Receptor Potential Vanilloid channels are a super-family of transient receptor potential (TRP) ion channels, that are selective for calcium and magnesium over sodium ions. Members of the family respond to noxious heat, cold, acid, osmolality and capsaicin, a vanilloid molecule derived from hot red peppers.
Nociceptive sensory neurones have many branches within the skin and some innervate blood vessels.
These branches liberate chemicals that cause vasodilatation and increase capillary permeability.
The "axon reflex" is not a proper reflex because there are no synapses in the neural pathway, but noxious stimulation induces redness and tissue swelling because of sensory impulses that release mediators in the blood vessel and cause the "flare". The flare occurs because of vasodilatation (redness) and increased permeability that results in the movement of plama proteins into the extracellular fluid.
Sensitization of unmyelinated afferent fibres
Sensitization occurs when an unmyelinated nerve sensory ending that is normally responsive only to extreme forces and movements, becomes sensitive to normal forces and movements.
One example of sensitization is inflammation: normally nociceptive nerve endings respond only to extreme forces and movements, but, once sensitized, they become much more sensitive and respond to normal movements. In both circumstances the messages they carry give rise to pain.
In an inflamed joint, a small movement can give rise to pain. IN this condition, the unmyelinated nerve endings can become sensitized, and instead of responding only to large forces and movements, become very sensitive to any movement- because these nerve endings are affected by chemicals produced within damaged tissues, such as
- Bradykinin, and
Chemicals with the ability to sensitize the nociceptive nerve endings are known as Endogenous Algesic Agents.
Some of the common over-the-counter analgesic drugs act by interfering with the production or action of these agents.
Endogenous Algesic Agents
Bradykinin is a peptide produced by enzymes released from damaged cells acting on a plasma protein, and is found in fluid in inflamed joints. The effects of Bradykinin include :
Prostaglandins (PGs) are released from injured cell membranes.
Arachadonic acid is broken down to prostaglandins by an enzyme (cyclo-oxygenase) to produce
- local oedema (extravasation of plasma proteins)
PGE, PGF2alpha and PGI. They have the following effects:
they induce vasodilatation
they increase capillary permeability to plasma proteins, - causing local oedema
they are all Algesic Agents
Neuropeptides in unmyelinated nerves.
Fine unmyelinated afferents contain neuropeptides which can sensitize sensory endings when they are released. These peptides attract cells of the immune system, cause vasodilatation and increased capillary permeability. These neuropeptides include:
Substance P may also be a neurotransmitter in the pain pathway in the dorsal horn of the spinal cord.
- Substance P
- Calcitonin gene-related peptide (CGRP)