PHYSIOLOGY OF PAIN

1. PHYSIOLOGY OF PAIN BY ABDULLAH RADWAN

2. CONTENTS • Definition • Peripheral aspects of pain • Central aspects of pain • Modulation of pain transmission • Gate control theory • Pain inhibition by opiates • Referred pain • Phantom limb pain

3. Definition • Pain is defined as an unpleasant sensory and emotional experience that is associated with actual or potential tissue damage. • It is a protective mechanism that alerts the individual to make an appropriate response to prevent further injury.

4. A) Peripheral aspects of pain • The types of sensory receptors responsible for the detection of painful stimuli are called nociceptors which are mostly found to be free nerve endings. • These free nerve endings are found in almost all types of tissues in the body.

5. The nociceptors give rise to two types of afferent nerve fibers: • Small diameter myelinated fibers- group III afferents, which conduct impulses at 5- 30 m/s, and are usually associated with sharp, pricking pain sensations- so called acute or fast pain. • Small diameter unmyelinated fibers- group IV afferents, which have a much slower conduction velocity (about 0.5- 2 m/s). These fibers are usually associated with longer lasting , dull or burning pain, so called chronic or slow pain.

6. Both types of nociceptors are ploymodal receptors in that they can respond to a variety of different stimuli- mechanical, thermal and chemical.

7. Chemical mediators of pain are released by damaged tissue and will activate the nociceptors. These include: Bradykinin, substance P, histamine, prostaglandins, and 5-hydroxytryptamine (5-HT). • These chemical mediators are also released in pathological situations such as inflammation, arthritis, coronary occlusion and ulceration. • They are responsible for the longer lasting aspects of pain once the initial physical stimulus has ceased.

8. B) Central aspects of pain • Both group III and group IV afferent fibers project to the spinal cord where they synapse with neurones in the dorsal horn of the gray matter of the spinal cord. • These neurones- transmission cells (or T cells)- project to higher centers of the nervous system via the spinothalamic tracts. • The T cells are therefore responsible for relaying peripheral information regarding pain sensation to the higher centers.

11. Modulation of pain transmission • The T cells, in addition to receiving excitatory input from the primary afferent nociceptive fibers, they are also subject to an inhibitory input from interneurones arising in the substantia gelatinosa (SG) of the spinal cord dorsal horn grey matter. • These SG interneurones, in turn are excited by input from large diameter, low threshold, mechanosensitive afferents. • The T cells therefore receive excitatory inputs from nociceptive afferents, and inhibitory inputs from large diameter mechanosensitive afferents- via SG cells.

12. The overall balance of the levels of excitatory and inhibitory influences on the T cells is of great importance in determining whether or not pain sensation is relayed to higher cognitive centers of the brain. • Therefore, activation of low threshold mechanoreceptors, whether by electrical or mechanical means, can inhibit the transmission of pain signals through the T cells by altering the balance of excitatory and inhibitory inputs to the cells.

13. Gate-control theory • This modulation of pain transmission by altering afferent input to the spinal cord is known as the gate-control theory which was established by Melzack and Wall in 1965. • In this theory, the activation of large diameter, myelinated axons in the periphery increases the amount of inhibition impinging on the T cells in the spinal cord via cells of the SG. • This inhibitory input caused by stimulation of large diameter, mechanosensitive afferents is said to ‘close the gate’ to pain transmission through the T cells in the spinal cord.

14. Gate-control theory • This theory has important implications for the management of pain in physical medicine. • Any technique that involves the activation of large diameter mechanosensitive afferents has the potential to modulate pain transmission in the spinal cord. • Techniques such as massage, joint manipulation, traction and compression, thermal stimulation and electrotherapy, all have the capability to produce sensory inputs from low threshold afferents, which can ultimately inhibit pain transmission in the spinal cord by “closing the gate” i.e. inhibiting T cell excitability via the substantia gelatinosa cells.

16. Pain inhibition by opiates • The inhibitory interneurones in the substantia gelatinosa of the spinal cord can also be influenced by descending inputs from higher brain centers. Stimulation of the periaqueductal grey matter and of the raphe nucleus in the medulla can produce analgesia by inhibiting transmission in the spinal cord. • These structures possess receptors for opiates and can be activated by drugs such as morphine. • Endogenous opiates such as enkephalins and enorphins also activate these structures to produce analgesia through descending influences on the inhibitory interneurones in the substantia gelatinosa.

17. Referred pain • It is pain felt at a site in the body elsewhere from the source of disease or injury. • An example of this is the anginal pain where the heart is the affected organ but pain is often described as arising in the upper chest, left shoulder and arm.

18. Referred pain • It is explained by the convergence of the afferent nerve fibers in the dorsal horn of the spinal cord. • These afferents are receiving inputs from several sources that are innervated by the same spinal segments e.g. (T1- T4) in the case of heart and left arm). • The transmission cells pass this nociceptive information to higher centers as pain impulses but the higher centers cannot distinguish the source of this information as being either cutaneous or visceral in origin. • Peripheral input from cutaneous receptors normally predominate and this may account for the pain sensation being incorrectly ascribed to the skin rather than the visceral organ.

21. Phantom limb pain • It is the pain associated with a missing limb when it has been amputated. • It is often described as burning, electric or cramping sensations, and may persist for many years after the loss of the limb. • Until recently, the dominant theory for cause of phantom limbs was irritation in the severed nerve endings (called "neuromas").. • This may set up abnormal patterns of discharge in the peripheral nerve fibers, particularly nociceptors, which are then relayed to higher centers and perceived as pain sensations arising in the areas these nerves formerly supplied.

22. Phantom limb pain • A recent explanation for phantom limb pain is that it is due to the activity of the neural networks in the higher centers of the brain. • These neural networks form the so called neuromatrix, the structure and function of which may be genetically determined and may be susceptible to inputs from peripheral structures. • This neuromatrix is not localized, but is widespread throughout the brain.

24. Thank you