Background & Aims

Offset analgesia (OA) is observed when pain relief is disproportionate to the reduction in noxious input [1], whereas spatial summation of pain (SSp) is defined by increases in pain with an increase in stimulation area [2]. This study aimed to investigate OA and SSp in polyneuropathy (PN) patients with self-reported pain, PN without self-reported pain, and healthy control participants. It was hypothesized that there would be no difference in OA and SSp effects between the two patient groups, but patients would differ from healthy controls. This hypothesis was based, first, on the assumption that peripheral fibers and not the pain itself may be crucial for inducing both OA [3] and SSp [4] and second, on the fact that both groups of PN patients have similar sensory profiles [5].

Methods

Patients with a distal symmetrical PN (painful PN: n=15, pain-free PN: n=15) as well as age and sex-matched healthy controls (n=20) were included in this cross-sectional study. The diagnosis was based on the consensus criteria for symmetrical polyneuropathy [6]. All participants underwent full quantitative sensory testing (QST). To measure the magnitude of the OA and SSp effect, the pain intensity of each thermal stimulus was assessed continuously using an electronic visual analog scale. Regarding the OA paradigm, two individually temperature-adjusted constant trials (CT), offset trials (OT), and baseline trials (BT) were performed on a randomly selected side of the dorsum of the foot for OA in both PN groups and the healthy control group. Furthermore, regarding the SSp paradigm, a CT with a smaller stimulation area was applied twice to contrast it with the previously described CT with a larger stimulation area.

Results

Data from 50 subjects (M=71.4, SD 9.2 years) were included in the analysis. Significant SSp effects were found for PN patients without pain (p=0.007), and healthy controls (p<0.001), but not for PN patients with pain (p>0.05). Regarding OA, a significant OA effect was only shown in healthy controls (p<0.001), but not in the two patient groups (p>0.05). No significant correlations between OA, SSp, and the QST parameters were demonstrated (p>0.05). Comparable sensory profiles were shown for both patient groups.

Conclusions

The results provide preliminary evidence that SSp might be impaired in patients with painful PN when compared to PN patients without pain and healthy controls, challenging the hypothesis of SSp determined by peripheral fibers. Nevertheless, the lack of OA effects in both patient groups indicates a peripheral influence on OA, whereby the sensory profile of patients was comparable.

References

[1] Grill JD, Coghill RC. Transient analgesia evoked by noxious stimulus offset. J Neurophysiol 2002;87:2205–2208.

[2] Quevedo AS, Coghill RC. Filling-In, Spatial Summation, and Radiation of Pain: Evidence for a Neural Population Code in the Nociceptive System. J Neurophysiol 2009;102:3544–3553.

[3] Naugle KM, Cruz-Almeida Y, Fillingim RB, Riley JL. Loss of Temporal Inhibition of Nociceptive Information Is Associated With Aging and Bodily Pain. J Pain 2017;18:1496–1504.

[4] Granovsky Y, Raz N, Defrin R. Electrophysiological and psychophysical correlates of spatial summation to noxious heat: the possible role of A-delta fibers. Exp Brain Res 2017;235:639–646.

[5] Forstenpointner J, Ruscheweyh R, Attal N, Baron R, Bouhassira D, Enax-Krumova EK, Finnerup NB, Freynhagen R, Gierthmühlen J, Hansson P, Jensen TS, Maier C, Rice ASC, Segerdahl M, Tölle T, Treede R-D, Vollert J. No pain, still gain (of function): the relation between sensory profiles and the presence or absence of self-reported pain in a large multicenter cohort of patients with neuropathy. Pain 2021;162:718–727.

[6] England JD, Gronseth GS, Franklin G, Miller RG, Asbury AK, Carter GT, Cohen JA, Fisher MA, Howard JF, Kinsella LJ, Latov N, Lewis RA, Low PA, Sumner AJ. Distal symmetrical polyneuropathy: definition for clinical research. Muscle Nerve 2005;31:113–123.

Presenting Author

Tibor M. Szikszay

Poster Authors

Tibor Szikszay

MSc

University of Luebeck

Lead Author

Wac?aw M. Adamczyk

PhD

The Jerzy Kukuczka Academy of Physical Education, Katowice, Poland

Lead Author

Kerstin Luedtke

University of Luebeck

Lead Author

Topics

  • Assessment and Diagnosis