Nociception

Pain is an unpleasant sensory and emotional experience. The physiology is complex and is located largely in the brain. In normal circumstances pain is elicited in the presence of actual or threatened tissue damage. The nervous system relays information to the brain about that tissue damage. However that information itself does not constitute pain, and is not pain until that information reaches the brain. Stimuli that elicits pain is commonly termed noxious. The information about tissue damage is referred to as nociceptive information. Most of what we know about pain relates to the physiology of nociception.

Transduction

Transduction means the detection of stimuli that might elicit pain. There are two basic mechanisms of transduction - chemical and mechanical nociception.

Chemical Nociception

a free nerve ending is stimulated by chemicals. Once stimulated, action potentials are generated in that nerve. The cardinal noxious chemicals capable of triggered a nerve and eliciting pain are bradykinin, serotonin, hydrogen ions, and potassium ions. These chemicals are released by cell damage as well as through inflammation.

Prostaglandins are also released by cell damage, but aren't able by in large to elicit nociceptive activity in nerve fibres. Prostaglandins facilitate the excitatory effect of the other chemicals.

Substance P is another chemical involved in the process of nociception. This chemical is located inside the terminals of peripheral nerve fibres. When the nerve fibre is stimulated by other chemicals, substance P is released. In the periphery substance P is unable to directly stimulate these nerve fibres. It acts to promote vasodilation, which enhances inflammation, which thereby will secondarily increase the release of the above noxious chemicals and therefore secondarily enhance the stimulation of the nerve fibres. The primary function of substance P is to heal tissue damage and is part of the nocifensive system - a combination of nociception and defensive.

Mechanical Nociception

This is less well understood and may occur when tissues that involve collagen are subjected to mechanical stress. Woven between collagen fibres are terminals of nociceptive nerve fibres. At rest the nerve fibres are able to pass through the weave of collagen easily. However when a tension is applied to the collagen, the spaces between the collagen fibres are constricted, and the nerve endings are compressed or stretched and are stimulated mechanically.

Peripheral Transmission

This includes events in peripheral nerve fibres once transduction has occurred. A response can be recorded from a peripheral nerve after a stimulus has been applied. The recording electrode experiences large changes in electrical potential. There are three major waves - A wave, B wave, and a smaller later C wave.

Velocities can be calculated through using the distances between the two electrodes. The diameters of myelinated (group A) nerve fibres are proportional to their conduction velocities, with a ratio of 6, i.e. the conduction velocity is equal to 6 times its diameter with appropriate adjustment of units.

Characteristics of sensory nerve fibres

Nerve fibre	Myelinated axons	Diameter (µm)	Conduction velocity (m/s)	Sensory information	Usefulness of electroneuromyography	Usefulness of QST
Aα	Yes	13-20	80-120	Proprioception, muscle spindle primary endings (Ia), golgi tendon organs (Ib) (and alpha motor neurons)	Yes (H reflex)	No
Aβ	Yes	6-12	33-75	Discriminative mechanoreception (touch, vibration), proprioception, pain modulation (block nociceptive information, allodynia in sensitisation)	Yes (sensory nerve conduction)	Yes
Aγ	Yes	4-8	15-40	Touch, pressure (and gamma motor neurons)		No
Aδ	Thin	1-5	3-30	"rapid" pain, crude touch, pressure, temperature. AMH type I for rapid mechanical pain (high heat threshold >53C), AMH type II for rapid heat pain (lower heat threshold 43-47C).	No	Yes
C	No	0.3-1.5	0.5-2.0	"slow" pain, touch, pressure temperature (and postganglionic autonomic). Polymodal.	No	Yes

The Aα and Aγ nerves are largely made up of motor neurons. The Aβ waves are produced by large diameter sensory nerve fibres that information related to proprioception, touch, and pressure. All fibres capable of transmitting nociception are Aδ fibres or C fibres.

There is no such thing as a "pain fibre" or specific nociceptive fibre. There are a variety of nerve fibres that are capable of transmitting nociception, but that may not be their only function. In various situations there may be more than one fibre involved in transmitting nociceptive information.

Nerves that transmit nociception have a threshold (called the noxious range) at which nociception occurs, and different nerves have different thresholds. For example there can be Aδ high threshold mechanoreceptors, and Aδ low threshold mechanoreceptors. Some mechanoreceptors are mixed in that they respond to both heat and mechanical information. Thermoreceptors respond to heat stimuli, but some do not have a linear increase in firing frequency in respond to increasing temperatures. C fibres are polymodal and can respond to chemical, thermal, or mechanical stimuli.

Central Transmission

Once information is detected by transduction, and passed along nerve fibres through transmission, it will reach the central nervous system.

The dorsal roots transmit all manner of sensory fibres. They can be divided into large diameter afferents and small diameter afferents. Large diameter afferents aren't involved in nociception, but rather convey other information such as proprioception and touch, and pass up the posterior faniculus. They do however send collateral branches into the dorsal horn.

All nociceptive afferent fibres are found in the small diameter afferent group. When they reach the spinal cord they don't go directly into the grey matter. They first send ascending and descending collateral through the dorsolateral tract of the spine. At various sites, collateral branches are released into the dorsal horn of the grey matter. In practical terms, nociceptive information reaching a segment is not restricted to that segment. A single nerve fibre conveying nociception can be distributed as far as 1-3 segments cephalad and 1-3 segments caudad.

Within the dorsal horn are neurons that pass upwards to more rostral regions of the central nervous system. They form the anterolateral funiculus (also known as the anterior and lateral spinothalamic tracts). The cell bodies of these neurons are mostly located within lamina V and lamina I of the dorsal horn. These second order neurons have connections higher up in the nervous system, and wait to receive information from the peripheral first order neurons.

Neurons in lamina I are called marginal neurons.

Interneurons are found within the dorsal horn which can inhibit first order neurons (pre-synaptic inhibition) and/or second order neurons (post-synaptic inhibition).

Inhibitory neurons in lamina II, the substantia gelatinosa, can modulate the influence of incoming peripheral nerve fibres.

Neurons in lamina V are called wide dynamic range neurons. They can respond to non-noxious mechanical stimulation via collateral branches from large diameter afferents. They can also respond to noxious information from C fibres.