Abstract
Primary hyperalgesia is characterized by increased responsiveness to
both heat and mechanical stimulation in the area of injury. By contrast,
secondary hyperalgesia is generally associated with increased responses
to mechanical but not heat stimuli. We tested the hypothesis that
sensitization in secondary hyperalgesia is dependent on the class of
peripheral nociceptor (C- or A-nociceptor) rather than the modality of
stimulation (mechanical vs heat). A- and C-nociceptors were selectively
activated using contact heat ramps applied to the hind paw dorsum in
animals with hind paw inflammation (primary hyperalgesia) and knee
inflammatory arthritis (secondary hyperalgesia). Sensitization to A- and
C-nociceptor activation in primary and secondary hyperalgesia was
assessed by reflex withdrawal thresholds and by Fos immunocytochemistry
in the dorsal horn of the spinal cord, as an index of neuronal
activation. In primary hyperalgesia, only C-nociceptor-evoked withdrawal
reflexes were sensitized. This was associated with increased spinal
lamina I neuronal activation to both A- and C-nociceptor activation.
Fos-like immunoreactivity (FLI) was unchanged in other dorsal horn
laminae. In secondary hyperalgesia, only A-nociceptor-evoked withdrawal
reflexes were sensitized, and FLI was increased in both superficial and
deep dorsal laminae. Neurons in the superficial dorsal horn receive and
process nociceptor inputs from the area of primary hyperalgesia,
resulting in functional sensitization to C-nociceptive inputs. In
inflammatory arthritis, secondary hyperalgesia is evoked by A-nociceptor
thermal stimulation, suggesting that secondary hyperalgesia is
A-nociceptor, rather than stimulus modality (mechanical vs thermal),
dependent. Fos-like immunoreactivity evoked by A-nociceptor stimulation
in secondary hyperalgesia suggests that the sensitization is underpinned
by spinal neuronal sensitization in laminae I and IV/V.
Original language | English |
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Pages (from-to) | 1074-1083 |
Number of pages | 10 |
Journal | PAIN |
Volume | 156 |
Issue number | 6 |
Early online date | 6 Mar 2015 |
DOIs | |
Publication status | Published - Jun 2015 |
Keywords
- hyperalgesia
- A - nociceptor
- c - fos
- spinal cord
- arthritis
- nociception
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Professor Bridget M Lumb
- School of Physiology, Pharmacology & Neuroscience - Professor of Systems Neuroscience
- Bristol Neuroscience
Person: Academic , Member