An introduction to pain pathway

Author: Dr Mohammad Shakiluzzaman

Introduction:

Pain is a type of stimulus that causes physical discomfort which may range from mild to severe and comprised of both physical & emotional component.  The International Association for the Study of Pain defines pain as “An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.” Pain is the vital function of nervous system by which body gets warning about potential & actual damage.

This article provides an overview of important pain pathways. Here discussion will be done on how the sensory apparatus of the body & system of signal transmission relate to pain and how different parts of pain pathway are used to reduce the intensity of pain. For this, it is Important to understand about, what are the constituents of total pain experience. It consists of:

1. Transduction of pain signal at the peripheral receptor site:

Naked, free nerve endings of primary afferent A-delta and C fibres are known as Nociceptors. They are the specialised sensory receptors responsible for the detection of noxious (unpleasant) or Painful stimuli. By the process called primary sensitisation, inflammatory mediators those released in response to tissue damage, (like bradykinin, serotonin, prostaglandins, cytokines, and H+) stimulates nociceptors. After got stimulated, Nociceptors transform the stimuli into electrical signals or action potential.

2. Transmission of pain signal along the peripheral nerve:

Electrical signals or action potential generated by the process of transduction, they are conducted to the central nervous system through the peripheral nerves. A-delta fibres are lightly myelinated which transmit signals rapidly in comparison to C fibres for rapid, sharp & localized pain. C fibres are unmyelinated which are relatively slower in signal transmission then A-delta fibres; transmit signals for slow, diffuse & dull pain.

The Primary afferent neurons have their cell body located in the dorsal root ganglion and their central processes enter the dorsal horn in the lateral division of the dorsal root. The first order neurons synapse with the second order neurons whose axon crosses the midline and the fibres ascend in the contralateral spinothalamic tract. They synapse with the third order neurons in Thalamus and their axons project into the somatosensory cortex. Some of the fibres project into the contralateral periaqueiductal grey matter. From peri-aqueductal grey matter descending inhibitory fibres start and some of the fibres project into different limbic nuclei. ^[1]

3. Pain perception at the supra spinal site:

During acute pain experience, a large brain network is activated. MRI has demonstrated that, in acute pain experience, the commonest areas activated are:  Primary and secondary somatosensory, insular, anterior cingulate cortex, prefrontal cortex and the thalamus are. These areas play important role in pain perception.

4. Modulation of pain at the level of spinal cord:

Modulation is neural process to reduce the activity in pain transmission system. There are many pain modulation systems, among those most important some are:

• Endogenous Pain Modulation System: By this system, endogenous opioids act on the opioid receptors of dorsal horn and results in presynaptic inhibition.
• Segmental Inhibition: By this system Glycin & GABA like neurotransmeitters locally inhibit the dorsal horn.
• Gate control theory of Pain: It states that activating the larger diameter A-Beta fibres leads to inhibition of pain signals transmitted via smaller diameter A-Delta & C fibres. An inhibitory interneuron acts as a physiological gate which is closed by stimulation of A-Beta fibres. In 1965 Malzack & Wall proposed this historical theory. ^[1]
• Descending Inhibitory Pathway: Serotonin & Norepinephrine activates inhibitory neurons situated in dorsal horn. They send an inhibitory signal in the dorsal horn & reduce the intensity of signal which is transmitted from first order neuron to the second order neuron. ^[1]

Key Points:

• By producing membrane-stabilizing effects with various agents, reduction of pain transduction can be obtained. By possessing membrane-stabilizing effects of nociceptors, their response to endogenous mediators of inflammation reduced by Cyclo-oxygenase inhibitors, Corticosteroids, tricyclic anti-depressants, and local anaesthetics. ^[3,4]
• Transmission of nociceptive impulses along the peripheral nerve can be blocked by the use of local anaesthetics ^[3,4]
• Nociceptive second-order neurons are profoundly suppressed by general anaesthetics and opioid analgesics.^[3,4]
• Effects of TENS, Spinal Cord Stimulation, Peripheral Nerve stimulation etc are based on Gate control theory.
• Anti-depressant medications help in reducing the intensity of pain by activating Descending Inhibitory Pathway. ^[1]
• Deeper limbic structures are associated with the affective motivation (emotional) component of pain. That’s why emotional effect of pain cannot be denied in pain management. ^[1]

Conclusion:

The total pain experience is the result of, nociceptive Transduction of pain signal at the peripheral receptor site, Transmission of pain signal along the peripheral nerve,  Pain perception at the supra spinal site,  Modulation of pain at the level of spinal cord, emotional reactions and associated sensations. Each analgesic agent and interventional pain management procedures have its own sites and mechanisms of action. To provide pain relief by administering such drugs and performing interventional procedures, optimum analgesia may be obtained. For this, understanding the pathway of pain, mechanism of action, effect of analgesics and interventional procedures over different level of pain pathway is very important.

References:

1. Gautam Das, MD, FIPP. (2017). Basics of Pain management, First Edition, CBS Publishers & Distributors Pvt Ltd.
2. Hains, B. (2007). Pain. Gray Matter. Chelsea House.
3. Reddi, D. (2018). [online] Ucl.ac.uk. Available at: https://www.ucl.ac.uk/anaesthesia/StudentsandTrainees/PainPathwaysIntroduction [Accessed 8 Jul. 2018].
4. Natasha Curran, D. (2018). [online] Ucl.ac.uk. Available at: https://www.ucl.ac.uk/anaesthesia/StudentsandTrainees/PainPathwaysIntroduction [Accessed 8 Jul. 2018].
5. Kitahata, L. (2018). Pain pathways and transmission.. [online] PubMed Central (PMC). Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2588883/ [Accessed 8 Jul. 2018].