Secondary Hyperalgesia Mediated by Nociceptive and Other Sensory Pathways
Secondary hyperalgesia occurs in the areas around the injured site because of nociceptor activation in the central nervous system.
In a new study reported in Pain, scientists from the Université Catholique de Louvain in Brussels, Belgium, found evidence that the effects of central sensitization extend beyond nociceptive pathways to other sensory modalities.1
Along with the primary hyperalgesia that results from activation of peripheral nociceptors in response to injury, secondary hyperalgesia occurs in the areas around the injured site as a result of nociceptor activation in the central nervous system.2 "Considering that the purpose of sensitization is to prevent further exposure of the injured body part to noxious stimuli, we postulated that...sensitization does not restrict itself to mechanisms acting on nociceptive pathways" but may also affect additional sensory modalities relevant to the site of injury, the researchers wrote. Lending support to this concept are earlier findings of hypersensitivity to various sensory stimuli in patients with fibromyalgia.3,4
In the current study, researchers tested this hypothesis by using high-frequency electrical stimulation (HFS) of the skin in 26 healthy participants (18 women; median age, 23 years). This technique has been shown to induce central sensitization and to increase cortical processing of visual stimuli projected onto the sensitized area.5 HFS has previously been found to enhance "responses to nonpainful vibrotactile stimuli conveyed via the dorsal columns," which persisted after 20 minutes but not after 45 minutes,6 suggesting that "changes induced by HFS involve multiple mechanisms, having distinct time courses," according to the investigators of the current study.
Immediately before the application of HFS to each participant's ventral forearm, and 20 and 45 minutes after HFS, they recorded EEG responses to visual stimuli projected with a laser onto the sensitized skin or the contralateral arm. Eye movements were tracked with an infrared camera to ensure that participants' gaze remained fixed on the projected stimuli.
Although mechanical hyperalgesia was observed both 20 and 45 minutes after the application of HFS, cortical responses to visual stimuli were found only at the 20-minute mark. Consistent with the hypothesis, these results show that intense nociceptive activation "does not only lead to a sensitization of nociceptive pathways but also induces changes in the cortical processing of visual stimuli projected onto the sensitized body part," the researchers reported.
They propose that these effects "result from supraspinal and multimodal mechanisms leading to an enhancement of the responses to stimuli that are relevant for the sensitized body part."
Summary and Clinical Applicability
In addition to its effect on nociceptive pathways, central sensitization appears to involve other sensory modalities relevant to the site of injury.
- DM Torta DM, Van Den Broeke EN, Filbrich L, Jacob B,Lambert J, Mouraux A. Intense pain influences the cortical processing of visual stimuli projected onto the sensitized skin. Pain. 2017;158(4):691-697. doi: 10.1097/j.pain.0000000000000816
- Loeser JD, Treede RD. The Kyoto protocol of IASP basic pain terminology. Pain. 2008; 137(3):473-477. doi: 10.1016/j.pain.2008.04.025
- Geisser ME, Glass JM, Rajcevska LD, et al. A psychophysical study of auditory and pressure sensitivity in patients with fibromyalgia and healthy controls. J Pain. 2008;9(5):417-422. doi: 10.1016/j.jpain.2007.12.006
- Wilbarger JL, Cook DB. Multisensory hypersensitivity in women with fibromyalgia: implications for well being and intervention. Arch Phys Med Rehabil. 2011;92(4):653-656. doi: 10.1016/j.apmr.2010.10.029
- Klein T, Magerl W, Hopf HC, Sandkuhler J, Treede RD. Perceptual correlates of nociceptive long-term potentiation and long-term depression in humans. J Neurosci. 2004;24(4):964-971. doi: 10.1523/JNEUROSCI.1222-03.2004
- van Den Broeke EN, Mouraux A. High frequency electrical stimulation of human skin induces heterotopical mechanicaland heat hyperalgesia and enhanced responses to vibrotactile input. J Neurophysiol. 2014;111(8):1564-1573. doi: 10.1152/jn.00651.2013