Highlights
- •Experimentally induced hyperalgesia in human models of neuropathic pain is short-lived.
- •Peri-incisional punctate hyperalgesia lasts for 4–8 weeks after inguinal hernia repair.
- •There are concomitant heat and cold detection deficits, which persist beyond 6 months.
- •Subacute incisional punctate hyperalgesia reflects central sensitization.
- •Measures of subacute punctate hyperalgesia may be useful in analgesic drug assays.
Abstract
Cutaneous mechanical hyperalgesia can be induced in healthy volunteers in early phase
analgesic studies to model central sensitization, a key mechanism of persistent pain.
However, such hyperalgesia is short-lived (a matter of hours), and is used only for
assessing only single drug doses. In contrast, postsurgical peri-incisional hyperalgesia
may be more persistent and hence be a more useful model for the assessment of the
efficacy of new analgesics. We undertook quantitative sensory testing in 18 patients
at peri-incisional and nonoperated sites before open inguinal hernia repair and up
to the 24th postsurgical week. The spatial extent of punctate hyperalgesia and brush
allodynia at the peri-incisional site were greatest at weeks 2 and 4, but had resolved
by week 24. Heat allodynia, suggestive of local inflammation or peripheral sensitization,
was not observed; instead, there were deficits in cold and heat sensory detection
that persisted until week 24. The findings suggest that central sensitization contributes
significantly to mechanical hyperalgesia at the peri-incisional site. The prolonged
duration of hyperalgesia would be advantageous as a pain model, but there was considerable
variability of mechanical hyperalgesia in the cohort; the challenges of recruitment
may limit its use to small, early phase analgesic studies.
Perspective
Peri-incisional mechanical hyperalgesia persists for ≥4 weeks after open inguinal
hernia repair and reflects central sensitization; this may have usefulness as a model
of chronic pain to assess the potential of antineuropathic analgesics.
Key words
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Article info
Publication history
Published online: April 18, 2019
Accepted:
March 11,
2019
Received in revised form:
February 2,
2019
Received:
July 8,
2018
Footnotes
Supported by an unrestricted educational grant from GlaxoSmithKline UK, and by the Cambridge National Institute of Health Research Biomedical Research Centre. D.W.W. and M.C.L. were in receipt of Medical Research Council (MRC) Research Training Fellowships. D.K.M. is supported by a National Institute of Health Research Senior Investigator Award. The authors declare no conflicts of interest. We acknowledge assistance from Lisa Law (previously based at MRC Biostatistics Unit at the University of Cambridge) for assistance with power calculations.
Supplementary data accompanying this article are available online at www.jpain.org and www.sciencedirect.com.
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© 2019 by the American Pain Society
