Article type
Year
Abstract
The chemical base of pain is best approached by considering that the amount of neural activity in nociceptive afferents [the distinct type of receptors located at the termination of free nerve endings of A-delta and C fibers] is influenced by two factors. These are (1) the intensity and duration of stimulation and (2) the micro-environment of the nociceptors.
The term micro-environment implicates the role of chemical substances in nerve transmission, which appear to act in two general capacities. The first, algesic or pain-producing substances, are either neurotransmitters or excitatory neuromediators. They include H*, K*, serotonin, histamine, prostaglandins, bradykinin substance P, substance K, the amino acids glutamate and aspartate, calcitonin gene related peptide, vasoactive intestinal peptide, cholesystokinin, adenosine triphosphate, and acetylcholine. These are all located in surrounding tissue, plasma, basophils, mast cell granules, and nerve terminals. By performing an excitatory action upon the membrane of nociceptors, these agents may also play an indirect role by altering local micro-circulation.
The second class of chemical substances, analgesic or pain-inhibiting substances, are inhibitory neuromediators. These include the endogenous opioids (enkephalins, dynorphins, and beta-endorphins), somatostatin, serotonin, norepinephrine, gamma-aminobutyric acid and neurotensin. Although generally associated with the descending pain control system, it is important to recognise that current research suggests that each neurotransmitter or neuromediator may have multiple actions in a given region, as demonstrated by substance P which has been found in both primary afferent terminals and descending axons. Several general distinctions may be made between neurotransmitters and neuromediators. The former may be located in the vicinity wherever peripheral nerve endings are located and display rapid actions that are of short duration. The latter, on the other hand, are more commonly associated with the central nervous system, have a slower onset of action, and may have more prolonged effects.
Although the neurochemistry of the central nervous system and of the dorsal horn in particular is extremely complex, its role can be more easily understood through the unifying concepts of the Gate Theory of pain proposed by Melzack and Wall1. Simply stated, the theory suggests that the nerve impulses which produce pain must pass through a series of gates en- route to the brain and that these gates are controlled by messages either descending from the brain or travelling towards the brain on other sensory fibers. These control mechanisms are all chemical and involve precise stereo-specific interactions of different classes of receptors with each of the neuromediators specified above. It is here where one can appreciate the role of conscious perception and the element of stress, which generate their own cascades of hormonal events which in turn either exacerbate of diminish the transmission [and thus the sensation] of pain. The Gate Theory also helps to explain why touch or mild mechanical stimulation may inhibit the transmission of pain messages, as the former afferents are believed to travel along large, last-conducting nerve fibers into the spinal cord, ultimately blocking the transmission of pain messages carried by smaller, slow-conducting fibres. The theory is also helpful in explaining the phenomena of sensitisation as well as "phantom pain,' the latter possibly produced by the destruction or alteration of receptors needed to sustain the inhibitory signalling requisite for modulating the sensation of pain.
At the cellular level, nerve transmission which leads to the sensation of pain also should be appreciated at the synaptic junction. For years, cell biologists have described the phenomenon of signal transduction and its effect upon the conveyance of nerve impulses from cell to cell. Its relevance to pain and pain management are topics to be outlined in this presentation. The applicability and power of these considerations is dramatically conveyed by the observations of Mannhelmer's group, who over the past decade have investigated the mitigating effects of epidural electrical stimulation upon episodes of angina in patients, most of whom have undergone bypass surgery2. These findings not only provide an elegant demonstration of the chemical models of pain presented at this symposium, but also have major implications in the potential effects of spinal manipulation at the hands of chiropractors. Understanding the basic chemical mechanisms of pain allows the physician to embark upon a therapeutic approach, regardless of whether that undertaking involves manipulation; pharmacologic agents (opiods, nonopiod and adjuvant analgesics); transcutaneous electrical nerve stimulation; acupuncture; massage; or relaxation, distraction, or cognitive techniques. It also helps us to understand the underpinnings of neuroplasticity, itself a concept which resonates with the basic tenets of chiropractic theory established over 100 years ago.
References
'Melzack R, Wall PD. Pain mechanisms: A new theory. Science 1965; 150: 971.
Mannheimer C, Eliasson T, Andersson B, Bergh CH, Augustinsson LE, Emanuelsson K, Waagstein F. Effects of spinal cord stimulation effected by pacing and possible mechanisms of action. British Medical Journal 1993; 307: 477-480.
The term micro-environment implicates the role of chemical substances in nerve transmission, which appear to act in two general capacities. The first, algesic or pain-producing substances, are either neurotransmitters or excitatory neuromediators. They include H*, K*, serotonin, histamine, prostaglandins, bradykinin substance P, substance K, the amino acids glutamate and aspartate, calcitonin gene related peptide, vasoactive intestinal peptide, cholesystokinin, adenosine triphosphate, and acetylcholine. These are all located in surrounding tissue, plasma, basophils, mast cell granules, and nerve terminals. By performing an excitatory action upon the membrane of nociceptors, these agents may also play an indirect role by altering local micro-circulation.
The second class of chemical substances, analgesic or pain-inhibiting substances, are inhibitory neuromediators. These include the endogenous opioids (enkephalins, dynorphins, and beta-endorphins), somatostatin, serotonin, norepinephrine, gamma-aminobutyric acid and neurotensin. Although generally associated with the descending pain control system, it is important to recognise that current research suggests that each neurotransmitter or neuromediator may have multiple actions in a given region, as demonstrated by substance P which has been found in both primary afferent terminals and descending axons. Several general distinctions may be made between neurotransmitters and neuromediators. The former may be located in the vicinity wherever peripheral nerve endings are located and display rapid actions that are of short duration. The latter, on the other hand, are more commonly associated with the central nervous system, have a slower onset of action, and may have more prolonged effects.
Although the neurochemistry of the central nervous system and of the dorsal horn in particular is extremely complex, its role can be more easily understood through the unifying concepts of the Gate Theory of pain proposed by Melzack and Wall1. Simply stated, the theory suggests that the nerve impulses which produce pain must pass through a series of gates en- route to the brain and that these gates are controlled by messages either descending from the brain or travelling towards the brain on other sensory fibers. These control mechanisms are all chemical and involve precise stereo-specific interactions of different classes of receptors with each of the neuromediators specified above. It is here where one can appreciate the role of conscious perception and the element of stress, which generate their own cascades of hormonal events which in turn either exacerbate of diminish the transmission [and thus the sensation] of pain. The Gate Theory also helps to explain why touch or mild mechanical stimulation may inhibit the transmission of pain messages, as the former afferents are believed to travel along large, last-conducting nerve fibers into the spinal cord, ultimately blocking the transmission of pain messages carried by smaller, slow-conducting fibres. The theory is also helpful in explaining the phenomena of sensitisation as well as "phantom pain,' the latter possibly produced by the destruction or alteration of receptors needed to sustain the inhibitory signalling requisite for modulating the sensation of pain.
At the cellular level, nerve transmission which leads to the sensation of pain also should be appreciated at the synaptic junction. For years, cell biologists have described the phenomenon of signal transduction and its effect upon the conveyance of nerve impulses from cell to cell. Its relevance to pain and pain management are topics to be outlined in this presentation. The applicability and power of these considerations is dramatically conveyed by the observations of Mannhelmer's group, who over the past decade have investigated the mitigating effects of epidural electrical stimulation upon episodes of angina in patients, most of whom have undergone bypass surgery2. These findings not only provide an elegant demonstration of the chemical models of pain presented at this symposium, but also have major implications in the potential effects of spinal manipulation at the hands of chiropractors. Understanding the basic chemical mechanisms of pain allows the physician to embark upon a therapeutic approach, regardless of whether that undertaking involves manipulation; pharmacologic agents (opiods, nonopiod and adjuvant analgesics); transcutaneous electrical nerve stimulation; acupuncture; massage; or relaxation, distraction, or cognitive techniques. It also helps us to understand the underpinnings of neuroplasticity, itself a concept which resonates with the basic tenets of chiropractic theory established over 100 years ago.
References
'Melzack R, Wall PD. Pain mechanisms: A new theory. Science 1965; 150: 971.
Mannheimer C, Eliasson T, Andersson B, Bergh CH, Augustinsson LE, Emanuelsson K, Waagstein F. Effects of spinal cord stimulation effected by pacing and possible mechanisms of action. British Medical Journal 1993; 307: 477-480.