Pain Perception Explored

Part of the survival value of pain is its association with learning centers in the brain. While nociceptive pain provides positive survival response to noxious stimuli, chronic pain has lost its value for this purpose.⁸² Hudspith MJ, Siddall PJ, Munglani R. Physiology of pain. In: Hemming HC, Hopkins PM, eds. Foundations of Anesthesia. 2nd ed. London, UK: Mosby; 2006. p267

The brain circuitry associated with both nociceptive and neuropathic pain involves areas considered to be essential in emotional learning, memory and reward.⁸³Apkarian AV. Pain perception in relation to emotional learning. Curr Opin Neurobiol. 2008. p464

Conditioned nociceptive response (CR) – learned pain

The neurons of the central nervous system not only have the capacity to transmit, inhibit and weigh information, but they may also store information for prolonged periods of time. Studies suggest that synaptic plasticity plays a role in pain pathways and may account for some forms of hyperalgesia, allodynia and analgesia.⁸⁴Sandkühler J. Learning and memory in pain pathways. Pain 88. 2000. p113.

The conditioning stimuli that induce synaptic long-term potentiation (LTP) in fine primary afferents are similar to those that trigger hyperalgesia. Further, spinal LTP and injury-induced hyperalgesia share signal transduction pathways, time course and pharmacological profile, which makes use-dependent LTP at Ad-and C-fiber synapses an attractive cellular model of injury-induced central sensitization and hyperalgesia. ⁸⁵Sandkühler J. Learning and memory in pain pathways. Pain 88. 2000. p114.

Nociceptive activation in the CNS

The insula and anterior cingulate, together with the thalamus and basal ganglion are activated in acute pain.⁸⁶Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain 2005. p463.

The brainstem and the descending pain modulatory system also play a role—where activity is observed in both the anticipation and perception of pain.⁸⁷Tracey I, Manty PW. The Cerebral Signature for Pain Perception and Its Modulation. Neuron, Volume 55, Issue 3, 377-391, 2 August 2007. p378, 382.

Hypervigilance

Anticipating pain is an adaptive response to noxious stimuli. However, for the chronic pain patient it becomes maladaptive and can lead to fear of movement, avoidance, anxiety, and so forth. Critical regions involved in amplifying or exacerbating the pain experience include the entorhinal complex, amygdalae, anterior insula, and prefrontal cortices. The degree of anticipation to a pain event positively correlates with the reported pain intensity across a group of healthy individuals, and this amplification is mediated in part via activity within the ventral tegmentum area of the brainstem and entorhinal cortex, as well as the periaqueductal gray matter (PAG).⁸⁸Tracey I, Manty PW. The Cerebral Signature for Pain Perception and Its Modulation. Neuron, Volume 55. 2007. p382

Neurodegenerative aspect of chronic pain

The prefrontal cortex is a site of major neurodegeneration and potential cell death in chronic pain patients, suggesting that severe chronic pain could be considered a neurodegenerative disorder that especially affects the PFC. This could in turn have consequent negative effects on the descending inhibitory system and contribute to their chronic pain state. These observations demonstrate that the brain in healthy subjects is distinct from those with chronic pain, indicating that chronic pain is at least partly a neurodegenerative disease.⁸⁹ Tracey I, Manty PW. The Cerebral Signature for Pain Perception and Its Modulation. Neuron, Volume 55, Issue 3, 377-391, 2 August 2007. 383