Pain is described by the International Association for the Study of Pain (IASP) as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”.
Pain is not only physical:
The perception of pain is so subjective and variable among patients. In order to make sense of the phenomenon, Cicely Saunders, a pioneer in UK hospice movements, brought in the concept of "total pain" in the 1960's. The theory addresses that pain is not only a form of suffering following physical injury(ies), but is also associated with the emotional and spiritual wellbeing of individuals. Her idea was a success and has transformed the practice of pain medicine, principally in the multi-disciplinary (MDT) management of chronic and palliative-care pain patients.
Pain is classified by its duration (acute/chronic/acute-on-chronic) and nature (nociceptive/non-nociceptive)
Acute versus chronic pain:
Acute pain is transient (i.e. less than 12 weeks in duration) and usually of an identifiable cause.
Post-operative pain from surgical incisions (in descending order of intensity: upper abdomen, thoracotomy, lower abdomen, limbs) and complications (e.g. wound infection, sepsis and abdominal distension) forms the major source of acute pain in hospital. The other potential causes include acute myocardial infarction, pancreatitis, ureteric colic, first-to-second degree burns and trauma.
Most inadequately treated acute pain may evolve into chronic pain, which by definition, lasts much longer and is "beyond the normal expected healing time for the injury". The nature and intensity of the original pain may vary due to the “wind-up phenomenon” and “peripheral or central sensitization”.
Nociceptive versus neuropathic pain:
Nociceptive pain arises from any "actual or threatened damage to non-neural tissue and is due to activation of nociceptors". The understanding of which shall require acquaintance of the four key stages of the pain pathway, pain fibres and the rexed laminae.
Neuropathic pain is resulted from “a lesion or disease of the somatosensory nervous system”. The disease process could happen centrally (e.g. multiple sclerosis, spinal cord pathologies) or peripherally (e.g. trigeminal neuralgia, post-herpetic neuralgia, diabetic- and post-traumatic neuropathies). We may further classify neuropathic pain by the aetiology of disease (e.g. over-pressure, degeneration, infection or inflammatory changes of the neuronal structures) and by the involvement of sympathetic nervous system (e.g. complex regional pain syndromes).
Axons in the peripheral nervous system:
The peripheral nerves are made up of a collection of nerve bundles with axons embedded in them. These axons are present in three major forms – A, B and C fibres. Their structures and functions are summarized below:
Students are reminded about the overlapping of functions between some peripheral nerve fibres.
The Rexed Laminae:
The grey matter of the spinal cord is divided into 10 functional layers – the Rexed Laminae. A clear understanding to laminae 1- 5 and 10 is crucial in pain medicine.
Laminae 1 to 5 are located in the dorsal horn and they are served as the main sites of synapse between the first- and second-order afferent neurons.
During a simple synapse, an action potential normally activates the voltage-gated calcium channel at the presynaptic cleft. The influx of calcium ions into the terminus of neuron potentiates exocytosis of neurotransmitters into the synaptic cleft, and by means of passive diffusion, the neurotransmitters may bind to their post-synaptic receptors to cause electropotential changes in the second-order neuron(s). Depending on the nature of the neurotransmitters, these changes could be excitatory (e.g. glutamate, substance P), inhibitory (e.g. GABA) or modulatory (e.g. noradrenaline, serotonin, opioids).
The second-order neurons are composed of three important cell types:
Putting Rexed laminae into application:
1. What do we already know?
Aδ fibres synapse at laminae 1 and 5; C fibres at 1 and 2.
2. What does histological evidence show?
Evidence suggests that cells in lamina 2 are showing considerable dendritic linkages between laminae 1, 5 and the rest of dorsal horn
3. What can we conclusion from the above?
An overwhelming Aβ signals produced by actions e.g. rubbing over the affected skin of pain, transcutaneous electrical nerve stimulation (TENS) could dampen the transmission of pain via Aδ and C to the higher center (See "Gate-control theory" by Melzack and Wall for further details).
The important stages of the pain pathway are transduction, transmission, perception and modulation. This model is particularly useful for the appreciation of the underlying mechanisms in acute pain.
Tissue damage triggers the release of “a soup of” pain and inflammatory mediators around the site of injury (e.g. prostaglandins, leukotrienes, substance P, mast cells, histamine, H+, K+, acetylcholine). These substances sensitize the surrounding nociceptors and activate their voltage-gated sodium channels.
Following successful depolarization, action potentials normally propagate along the axon; through the dorsal root ganglion (DRG), lissauer’s tract and into the dorsal horn for synapse at the rexed laminae.
The route of pain transmission “above the neck” is dissimilar to the above. Their nociceptive impulses are united at the trigeminal ganglion and then relayed to the medulla for synapse with the higher center.
Central transmission and perception of pain in the higher centre:
The three major ascending tracts that mediate pain from the periphery to high centers are named as follows:
Neo-spinothalamic tract forms a “direct connection” with the thalamic nuclei and sensory cortex of the brain, hence, provides the fast and pinprick sensations of pain immediately following the injury.
The other two ascending tracts tend to give off “collaterals” to the brainstem, thalamus and other cortical area as they ascend along the spinal cord:
Paleo-spinothalamic tract transmits the slow and dull characteristics of pain. It also stimulates brainstem nuclei to activate the descending pathway for pain modulation.
Archi-spinothalamic tract has collaterals that innervate hypothalamus and the limbic system. It is so predicted by experts that this tract could infleuence autonomic nervous system; and also the emotional and behavioral responses to pain.
Modulation and the descending pathways of pain:
This is rather complex and is thought to occur at multi-level. To simplify, the modulation of pain mostly occurs:
The principal brainstem nuclei contributory to the descending tracts are the peri-aqueduct grey (PAG) matter, locus coeruleus (LC) and nucleus raphae magnus (NRM).
PAG activates the serotonergic (5-HT) pathway of NRM. Together with the noradrenergic pathway of LC, their projections descend along the dorsal horn to interact with the primary nociceptive- and inter-neurons.
The modulatory substances that these fibres release, mostly in form of opioids and serotonin, are suggested to prevent the transmission of pain by inhibiting exocytosis of neurotransmitters from the primary-order neurons.
The remaining contents of the descending tracts are hypothesised to excite interneurons at rexed lamina 2, a.k.a. substantial gelatinosa, and thus to cause interruptions of pain transmission between laminae 1 and 5.
A statisfactory pain regimen would require:
The essence of pain management is to achieve "balanced analgesia" – an approach that maximizes therapeutic benefits of a combination of analgesic agents at their lowest possible doses, thereby to reduce side effects.
Rosalind Haire has produced some useful revision notes on "analgesics" in the prescribing chapter, which features the WHO pain ladder and drug formularies of paracetamol, non-steroidal anti-inflammatory drugs and opioid-based medications (http://www.fastbleep.com/medical-notes/other/21/50/525). This article therefore aims not to repeat the similar principles again
Possible sites of analgesia:
Locally at or near the site of injury:
Distally to the site of injury:
Gastrointestinal & Urinary:
LAST BUT NOT LEAST - CHRONIC PAIN!
This article explores the basic science behind the management of pain, with angle slightly inclined to acute pain. It is important for students to recall the 4 physiological mechanisms of pain, i.e. transduction, transmission, perception and modulation and to apply the knowledge to their actual clinical practice e.g. NSAIDs are used to reduce the soup of inflammatory mediators of pain and to relief sensitization; local anaesthetics are used to prevent formation of an action potential thereby dampen the transmission of pain etc.
Topic recommended to future reading would include opioid-related medical emergencies e.g. overdose, respiratory depression, urinary retention etc, the wind-up phenomenon of chronic pain and prescribing guidance for chronic pain, particularly in opioid conversion. There is also a merit to find out more about the surgical managements for difficult chronic pains.
Matthew Thakur has published an excellent article on the "neurobiology of pain". His article discusses the pathophysiology of pain in much more detail and can be accessed via: http://www.fastbleep.com/biology-notes/39/142/888
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