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Updated: Jul 6, 2026

Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
Published on: October 6, 2022
Enhancement of offset analgesia during sequential testing
1University of Birmingham, School of Psychology, Edgbaston, B15 2TT, UK. s.w.derbyshire@bham.ac.uk
Abstract:
Interruption of a continuous noxious heat by a relatively greater noxious heat evokes reductions in pain experience when the original noxious heat returns. The reduction is greater than that evoked by continuous delivery of noxious heat. This disproportionate reduction in pain experience, known as offset analgesia, is presumably mediated by a mechanism different to adaptation or habituation. Reduction in pain experience to an equivalent noxious stimulus, however, has also been demonstrated when applying the same stimulus over a number of days. This reduction due to repeated days of stimulation is known as attenuation. In order to distinguish further the mechanisms of offset analgesia and attenuation we applied noxious heat resulting in an experience of low, medium or high pain to the volar forearm of 16 subjects comparing pain intensity ratings for increases and decreases in temperature, repeated over 3 days. Offset analgesia was consistently demonstrated but the effects of attenuation were more complex. There was no attenuation effect for the unchanging stimuli delivered across the 3 days of testing but attenuation effects enhanced the offset analgesia resulting in a larger offset analgesia effect on days 2 and 3. It is possible that offset analgesia and attenuation are mediated by inter-related mechanisms. Further studies might investigate whether offset analgesia involves inhibitory structures such as the PAG-RVM.
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