Question 12

Define pain. Outline the processes by which pain is detected in response to a peripheral noxious stimulus.

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College Answer

Starting with the WHO definition of pain, followed by a brief description of the nature of noxious stimuli (thermal, mechanical, chemical) then proceeding to mention the nature of the cutaneous receptors would have been a very good start to this question. Following this, a description of the various substances involved in pain (K, prostaglandins, bradykinin, serotonin, substance P) and outlining the types of nerve fibres involved in pain transmission and how they synapse in the spinal cord and cortex was expected. The presence and nature of the descending inhibitory pathways was mentioned by very few.


  • Pain is "an unpleasant sensory or emotional experience associated with actual or potential tissue damage, or described in terms of such damage".
  • Nociceptor transduces a painful stimulus into an action potential:
  • Noxious stimuli sensed by these endings include:
    • Mechanical deformation
    • Acidity (pH <5.0)
    • Temperature (heat as well as cold)
    • Inflammatory mediators (eg. prostaglandins, bradykinin)
    • Contents spilled from damaged cells (eg. ATP)
  • Nociceptive transduction is process in which environmental stimuli evoke conformational changes in the structure of specific proteins located on nociceptor terminals that directly or indirectly (i.e., via cellular signalling cascades) trigger the opening or closing of ion channels.
  • From the nociceptor, the action potential travels along a pain fibre
    • 20 m/s along a myelinated Aδ fibre
    • 2m/s along an unmyelinated C fibre
  • Past the body of the neuron, which lies in the dorsal root ganglion
  • Into the spinal cord via the dorsal root
  • Up (or down) the tract of Lissauer
  • Into the dorsal horn grey matter
  • Here, the primary afferents synapse with dorsal horn neurons, which:
    • Are arranged into discrete laminae which correspond to different spatial and functional groups
    • Are influenced by excitatory and inhibitory interneurons the activity of which is regulated by descending projections from the brain
  • Dorsal horn neurons then send projections across midline to the contralateral spinal cord, where their fibres form the ascending spinothalamic tract
  • The spinothalamic tract fibres synapse with tertiary neurons in the thalamus
    • The thalmus is responsible for sensory mapping and cortical representation of the geographical position of the pain information, and it also regulates some of the affective response to pain
  • They also project to multiple other higher centres:
    • Nucleus of the solitary tract and caudal ventrolateral medulla (cardiovascular response to pain)
    • Periaqueductal grey matter (descending regulation of pain signals)
    • Lateral parabrachial area (emotional and affective response to pain)


Almeida, Tatiana F., Suely Roizenblatt, and Sergio Tufik. "Afferent pain pathways: a neuroanatomical review.Brain research 1000.1-2 (2004): 40-56.

Todd, Andrew J. "Neuronal circuitry for pain processing in the dorsal horn." Nature Reviews Neuroscience 11.12 (2010): 823-836.

Hudspith, Michael J., Philip J. Siddall, and Rajesh Munglani. "Physiology of pain." Foundations of anesthesia (2006): 267-285.

Steeds, Charlotte E. "The anatomy and physiology of pain." Surgery (Oxford) 27.12 (2009): 507-511.

Renn, Cynthia L., and Susan G. Dorsey. "The physiology and processing of pain: a review." AACN Advanced Critical Care 16.3 (2005): 277-290.


Kendroud, Sarah, et al. "Physiology, nociceptive pathways." StatPearls [Internet] (2020).

Cohen, Milton, John Quintner, and Simon van Rysewyk. "Reconsidering the International Association for the Study of Pain definition of pain." Pain reports 3.2 (2018).