Central sensitization and secondary hyperalgesia

Patients with neuropathic pain do not only show negative symptoms (i.e. a sensory deficit) related to the impairment of somatosensory pathways. Instead, they also show, paradoxical positive symptoms (ongoing pain, hyperalgesia and allodynia), indicating an increased responsiveness of nociceptive pathways. A prominent positive sign of neuropathic pain is increased sensitivity to noxious mechanical stimulation (mechanical or pinprick hyperalgesia). At present, there is no reliable and objective laboratory toolto assess these changes in the neural responsiveness to mechanonociceptive input. The mechanisms underlying these positive symptoms are different from those underlying the negative symptoms, and involve activity-dependent changes in both the peripheral and the central nervous system. Some patients can have a severe impairment without positive symptoms, while other patients can have a mild impairment but severe positive symptoms.

The mechanical hyperalgesia observed in patients with neuropathic pain is very similar to the mechanical hyperalgesia that can be induced by the sustained activation of nociceptors in healthy volunteers ("secondary hyperalgesia"). There is convincing evidence that mechanical hyperalgesia results from a facilitation of nociceptive transmission at the level of the spinal cord, i.e. central sensitization.

In an attempt to develop a biomarker for central sensitization, we recently conducted a study in which we recorded pinprick evoked brain potentials (PEPs) in the area of experimentally induced secondary mechanical hyperalgesia in healthy volunteers. We showed that when pinprick stimuli are applied in the area of secondary mechanical hyperalgesia, PEPs were significantly increased as compared to the responses elicited by stimulation of normal skin. Moreover, in a second study, we showed that this enhancement of PEPs is long lasting and follows the same time course as the mechanical hyperalgesia. These promising results suggest that the recording of PEPs could be used as a diagnostic tool to assess the positive symptoms of neuropathic pain.

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Researchers involved

Publications

2021

How different experimental models of secondary hyperalgesia change the nociceptive flexion reflex.

Clin Neurophysiol

Leone C, Di Lionardo A, Di Pietro G, Di Stefano G, Falco P, Blockeel AJ, Caspani O, Garcia-Larrea L, Mouraux A, Phillips KG, Treede RD, Truini A.

32(12):2989-2995.

2021

High-frequency electrical stimulation of cutaneous nociceptors differentially affects pain perception elicited by homotopic and heterotopic electrical stimuli

J Neurophysiol

van den Broeke EN, Urdi M, Mouraux A, Biurrun Manresa J, Torta DM

126(4):1038-1044.

2021

Human surrogate models of central sensitization: a critical review and practical guide

European Journal of Pain

Quesada C, Kostenko A, Ho I, Leone C, Nochi Z, Stouffs A, Wittayer M, Caspani O, Finnerup NB, Mouraux A, Pickering G, Tracey I, Truini A, Treede RD, Garcia-Larrea L.

25(7):1389-1428.

2020

Perceptual correlates of homosynaptic long term potentiation in human nociceptive pathways: a replication study

Royal Society Open Science

van den Broeke EN, Vanmaele T, Mouraux A, Stouffs A, Biurrun-Manresa J, Torta DM

8(1):200830.

2020

Within- and between-session reliability of secondary hyperalgesia induced by electrical high-frequency stimulation

European Journal of Pain

Cayrol T, Lebleu J, Mouraux A, Roussel N, Pitance L, van den Broeke E.

24(8):1585-1597.

2020

Burst-like conditioning electrical stimulation is more efficacious than continuous stimulation for inducing secondary hyperalgesia in humans

Journal of Neurophysiology

Gousset S, Mouraux A, van den Broeke EN.

123(1):323-328

2020

The focus of spatial attention during the induction of central sensitization can modulate the subsequent development of secondary hyperalgesia

Cortex

Filbrich L, van den Broeke E, Legrain V, Mouraux .

124:193-203

2019

Heterosynaptic facilitation of mechanical nociceptive input is dependent on the frequency of conditioning stimulation

Journal of Neurophysiology

van den Broeke EN, Gousset S, Bouvy J, Stouffs A, Lebrun L, van Neerven SGA, Mouraux A.

122(3):994-1001

2019

Central sensitization in humans: Popular phrase or useful concept?

Journal of Psychosomatic Research

van den Broeke EN, Van den Bergh O.

119:51-52

2019

Central sensitization increases the pupil dilation elicited by mechanical pinprick stimulation

Journal of Neurophysiology

van den Broeke EN, Hartgerink DM, Butler J, Lambert J, Mouraux A.

121(5):1621-1632

2018

No evidence of widespread mechanical pressure hyperalgesia after experimentally-induced central sensitization via skin nociceptors

Pain Reports

Cayrol T, Pitance L, Roussel N, Mouraux A, van den Broeke EN.

3(6): e691

2018

Central sensitization and pain hypersensitivity: some critical considerations

F1000 Research

van den Broeke EN.