TY - JOUR
T1 - A back-translational study of descending interactions with the induction of hyperalgesia by high-frequency electrical stimulation in rats and humans
AU - Patel, Ryan
AU - Taylor, Joseph
AU - Dickenson, Anthony
AU - McMahon, Stephen
AU - Bannister, Kirsty
N1 - Publisher Copyright:
© 2024 Lippincott Williams and Wilkins. All rights reserved.
PY - 2024/8/19
Y1 - 2024/8/19
N2 - In humans and animals, high-frequency electrocutaneous stimulation (HFS) induces an “early long-term potentiation-like” sensitisation, where synaptic plasticity is underpinned by an ill-defined interaction between peripheral input and central modulatory processes. The relative contributions of these processes to the initial pain or nociceptive response likely differ from those that underpin development of the heightened response. To investigate the impact of HFS-induced hyperalgesia on pain and nociception in perception and neural terms, respectively, and to explore the impact of descending inhibitory pathway activation on the development of HFS-induced hyperalgesia, we performed parallel studies utilising identical stimuli to apply HFS concurrent to (1) a conditioned pain modulation paradigm during psychophysical testing in healthy humans or (2) a diffuse noxious inhibitory controls paradigm during in vivo electrophysiological recording of spinal neurones in healthy anaesthetised rats. High-frequency electrocutaneous stimulation alone induced enhanced perceptual responses to pinprick stimuli in cutaneous areas secondary to the area of electrical stimulation in humans and increased the excitability of spinal neurones which exhibited stimulus intensity–dependent coded responses to pinprick stimulation in a manner that tracked with human psychophysics, supporting their translational validity. Application of a distant noxious conditioning stimulus during HFS did not alter perceived primary or secondary hyperalgesia in humans or the development of primary or secondary neuronal hyperexcitability in rats compared with HFS alone, suggesting that, upon HFS-response initiation in a healthy nervous system, excitatory signalling escapes inhibitory control. Therefore, in this model, dampening facilitatory mechanisms rather than augmenting top-down inhibitions could prevent pain development.
AB - In humans and animals, high-frequency electrocutaneous stimulation (HFS) induces an “early long-term potentiation-like” sensitisation, where synaptic plasticity is underpinned by an ill-defined interaction between peripheral input and central modulatory processes. The relative contributions of these processes to the initial pain or nociceptive response likely differ from those that underpin development of the heightened response. To investigate the impact of HFS-induced hyperalgesia on pain and nociception in perception and neural terms, respectively, and to explore the impact of descending inhibitory pathway activation on the development of HFS-induced hyperalgesia, we performed parallel studies utilising identical stimuli to apply HFS concurrent to (1) a conditioned pain modulation paradigm during psychophysical testing in healthy humans or (2) a diffuse noxious inhibitory controls paradigm during in vivo electrophysiological recording of spinal neurones in healthy anaesthetised rats. High-frequency electrocutaneous stimulation alone induced enhanced perceptual responses to pinprick stimuli in cutaneous areas secondary to the area of electrical stimulation in humans and increased the excitability of spinal neurones which exhibited stimulus intensity–dependent coded responses to pinprick stimulation in a manner that tracked with human psychophysics, supporting their translational validity. Application of a distant noxious conditioning stimulus during HFS did not alter perceived primary or secondary hyperalgesia in humans or the development of primary or secondary neuronal hyperexcitability in rats compared with HFS alone, suggesting that, upon HFS-response initiation in a healthy nervous system, excitatory signalling escapes inhibitory control. Therefore, in this model, dampening facilitatory mechanisms rather than augmenting top-down inhibitions could prevent pain development.
KW - Conditioned pain modulation
KW - Quantitative sensory testing
KW - Secondary hyperalgesia
KW - High-frequency electrocutaneous stimulation
KW - In vivo electrophysiology
KW - Dorsal horn
KW - Wide dynamic range
KW - Diffuse noxious inhibitory controls (DNIC)
UR - http://www.scopus.com/inward/record.url?scp=85201480755&partnerID=8YFLogxK
U2 - 10.1097/j.pain.0000000000003166
DO - 10.1097/j.pain.0000000000003166
M3 - Article
SN - 0304-3959
VL - 165
SP - 1978
EP - 1989
JO - Pain
JF - Pain
IS - 9
ER -