Gate Theory of Pain Modulation
Pain is a constant nuisance to many individuals. It can be a representation of actual injury (such as blunt force trauma to a limb) or emotional injury (such as the pain of a broken heart). As such, pain can be defined as a subjective perception of noxious stimuli. The International Association for the Study of Pain coined a more appropriate definition to encompass the above mentioned concept:
- Pain is an unpleasant sensory or emotional experience associated with actual or potential tissue damage, or described in terms of such damage.
Pain can be classified temporally (acute versus chronic) or based on the site of origin (visceral versus somatic). Acute pain, as the name suggests, occurs suddenly and usually follows very recent insult (iatrogenic trauma, myocardial infarction). Chronic pain has a more protracted course progressing over months to years. It may be further subdivided into nociceptive and neuropathic pain, based on the cause of the injury along the neuronal pathway. Nociceptive pain results from stimuli that can result in tissue damage. Possible causes of nociceptive pain include sickle cell crises, sports injuries, mechanical pain or postoperative pain. On the other hand, neuropathic pain is a result of dysfunction of the nervous system or a lesion within the same. This is the typical pain felt in cases of trigeminal neuralgia, diabetic neuropathy, and cancer. It is possible that both nociceptive and neuropathic type pains can occur simultaneous to give a mixed type pain.
Pain originating from internal organs – also called visceral pain – is often described as a dull, aching or throbbing pain that cannot be localized. The difficulty with localizing the source of visceral pain stems from a phenomenon known as referred pain. This is a situation in which pain originating from one part of the body is perceived elsewhere. For example, pain associated with pancreatitis is often felt in the epigastrium (around the region of the xiphoid process) and radiating to the back. Another (more familiar) example is the pain associated with myocardial infarction, which is said to radiate up the left side of the neck, towards the left shoulder and along the left arm. This differs significantly from somatic pain, which arises from cutaneous and subcutaneous tissue, as well as musculoskeletal structures. The exact location of this type of pain can be localized to an exact point.
This article aims to look at the anatomical structures associated with pain perception in addition to examining the Gate Theory of Pain modulation.
The process of converting noxious stimuli into action potentials involves several steps. Firstly, tissue damage can occur secondary to chemical, thermal or mechanical insults. These events are detected by nociceptors; which are Aδ (A-delta; myelinated with a conduction rate of 20 m/s) and C (unmyelinated with a conduction rate of 2 m/s) fibers. The Aδ fibers transmit pain stimuli at a faster rate than C fibers. As a result, Aδ fibers is involved in protective spinal reflex arcs that causes individuals to withdraw from a noxious stimulus; while C fibers facilitate the transduction of slow, burning type pain. In response to the stimuli, nociceptors transduce this information into nerve impulses by releasing a myriad of neurotransmitters such as prostaglandins, bradykinins, substance P and histamine, which all promote an inflammatory response and simultaneously propagate pain signals to the spinal cord.
The action potential associated with this event is propagated along the nociceptors and carried to the dorsal horn of the spinal cord. Within the dorsal horn of the spinal cord, the nociceptors diverge cranially and caudally for two to three spinal segments, forming the dorsolateral tract of Lissauer. At these levels, nociceptors (first order neurons) then synapse with the cell bodies of the fibers of the spinothalamic tracts (second order neurons) at varying layers of the dorsal column known as Rexed laminae:
- Rexed lamina I (dorsomarginal nucleus) – responding to thermal or noxious stimuli to the skin.
- Rexed lamina II (substantia gelatinosa) – believed to regulate sensory input.
- Rexed laminae IV – VI (nucleus proprius) – also called the deep dorsal column nuclei, these cells respond to cutaneous stimuli as well as afferent information from visceral and deep somatic receptors.
- Rexed laminae VII & VIII – are responsible for transmitting deep somatic stimuli from muscles and joints.
The fibers of the spinothalamic tract leave the dorsal column and decussate in the anterior white commissure of the cord. Fibers concerned with pain and thermal sensation coalesce in the lateral funiculus (with the ventral spinocerebellar tract forming its lateral border) to form the lateral spinothalamic tract. Those fibers concerned with light touch and pressure sensation congregate in the anterior funiculus to form the ventral spinothalamic tract. These tracts have a somatotopic arrangement from lateral to medial: sacral fibers, lower limb fibers, trunk fibers and upper limb fibers. This arrangement is maintained throughout the ascending circuit. The spinothalamic tract takes this information to several central points for integration and processing. It gives off the spinoreticular fibers, which in turn synapse with neurons of the nucleus raphe magnus in the medulla oblongata. At the level of the midbrain, it gives branches that synapse with cells of the periaqueductal grey matter, nucleus raphe dorsalis, and the reticular formation. The rest of the fibers of the tract terminate in the ventral posterolateral and intralaminar nuclei of the thalamus.
From the thalamus, third order neurons travel through the posterior limb of the internal capsule and terminate at corresponding somatotopic areas of the somatosensory cortex (Brodmann area 3, 1, 2). The cerebral cortices not only allow conscious perception of pain, but it also stimulates the hypothalamus, amygdala and periaqueductal grey matter, which in turn inhibits pain transmission via the release of endogenous opioids, norepinephrine and γ-aminobutyric acid (GABA).
In 1965, Melzack & Wall theorized that there were systems in place that modified the passage of impulses that travel along afferent (including nociceptive) pathways. The basic concept of gate theory is that the activity of inhibitory interneurons suppress the ascending nociceptive signals and act like gates to decrease transmission. They postulated that small unmyelinated afferent fibers inhibit interneurons but excite cells of the spinothalamic tract; while larger afferent cells (such as those arising from touch corpuscles and hairs) excite the large neurons of lamina IV and interneurons of substantia gelatinosa. The previously mentioned interneurons are nerve fibers that complete the complex reflex arcs within the grey matter of the spinal cord. Rexed lamina II or the substantia gelatinosa is believed to house interneurons that regulate the transmission of pain by inhibiting transmission along both small and large diameter afferent fibers. When activated, they inhibit subsequent afferent fibers that form synapses with tract cells. As a result, bouts of low frequency afferent transmission along small fibers results in inhibition of the interneurons of substantia gelatinosa cells. As a result, afferent sensation from the large diameter fibers travel unopposed (albeit intermittently) to the spinothalamic tract cells of lamina IV. Hence the “gate” to lamina IV would be sporadically opened. This results in an initial large transmission along the large fibers that would gradually taper off as the “gate” closes (small afferent activity decreases).
On the contrary, if the impulses arising from the small afferent fibers were strong and persistent, the “gate” would be opened and a high volume of stimuli would be transmitted to lamina IV cells. This would therefore result in a greater degree of supraspinal perception of pain.