Mechanisms of Hyperalgesia and Hypoalgesia

Mechanisms of Hyperalgesia and Hypoalgesia

Sensitization of both peripheral and central afferents is responsible for the transition from normal to aberrant pain perception in the central nervous system that outlasts the noxious peripheral stimulus. For example, sustained noxious input from an active myofascial trigger point may sensitize dorsal horn neurons, leading to hyperalgesia and allodynia, as well as generating expanded referred pain regions. A possible explanation for this phenomenon is increased synaptic efficiency through activation of previously silent synapses at the dorsal horn.76Jay P. Shah, MD, Elizabeth A. Gilliams, BA. Uncovering the biochemical milieu of myofascial trigger points using in vivo microdialysis: An application of muscle pain concepts to myofascial pain syndrome. Bodywork and Journal of Movement Therapies, June 2008, p375.

How does hyperalgesia develop?

Spread of hyperalgesia is likely due to central sensitization of nociceptive neurons in the spinal cord by primary nociceptive afferent input (neurogenic hyperalgesia), which is the basis of secondary hyperalgesia in the vicinity of any site of injury.77Baumgärtner U, Magerl W, Klein T, Hopf HC, Treede RD. Neurogenic hyperalgesia versus painful hypoalgesia: two distinct mechanisms of neuropathic pain. Pain. 2002 Mar;96(1-2), p142

Synaptic plasticity phenomena associated with hyperalgesia and allodynia in pathological pain states are not restricted to the synapse between nociceptive afferents and second-order spinal neurons, but are potentially operational in several brain regions that process the sensory and affective components of pain, including the thalamus, somatosensory cortex, anterior cingulate cortex, hippocampus, and the amygdala.78Hartmann B et al. The AMPA Receptor Subunits GluR-A and GluR-B Reciprocally Modulate Spinal Synaptic Plasticity and Inflammatory Pain. Neuron, Vol. 44, 637–650, November 18, 2004, p643.

The interdependence of peripheral and dorsal horn can affect sensitization processes. Positive feedback of noxious signaling within the nervous system can also occur with inhibitory circuits, resulting in hypoalgesia or analgesia.79Chapman CR et al. Pain and Stress in a Systems Perspective. J Pain. 2008 February; 9(2): p21.

Types of hyperalgesia

Changes that occur in the periphery following trauma lead to peripheral sensitization and primary hyperalgesia. However, the altered processing of sensory input associated with trauma, inflammation, or nerve injury can only be partly explained by peripheral changes. Following injury, there is increased responsiveness to normally innocuous mechanical stimuli (allodynia) in a zone of secondary hyperalgesia in uninjured tissue surrounding the site of injury. In contrast to the zone of primary hyperalgesia, these changes are the behavioral manifestation of central sensitization associated with an expansion in receptive field size and a reduction in threshold of wide dynamic range (WDR) neurons.80Hudspith MJ, Siddall PJ, Munglani R. Physiology of pain. In: Hemming HC, Hopkins PM, eds. Foundations of Anesthesia. 2nd ed. London, UK: Mosby; 2006. p276.

Assessing & diagnosing

Similar or even identical pain symptoms can evolve in a variety of diseases. Symptoms can also vary considerably within the same disease, requiring classification of neuropathic pain states according to the underlying mechanisms rather than the precipitating disease. 81Baumgärtner U, Magerl W, Klein T, Hopf HC, Treede RD. Neurogenic hyperalgesia versus painful hypoalgesia: two distinct mechanisms of neuropathic pain. Pain. 2002 Mar;96(1-2), p150

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