Background & Aims
Experimentally-induced central sensitization leads to an area of secondary mechanical hyperalgesia (SMH) around the stimulation area through spinal facilitation of mechanonociceptive input.1,2 It has been shown that individuals with chronic pain develop more pronounced area of experimentally-induced SMH compared to healthy controls.3–6 However, even in pain-free, healthy participants, the spatial extent of SMH varies substantially and it remains unknown what pre-existing factors contribute to this variability. Therefore, this study aimed to explain the variability of experimentally-induced SMH area in healthy participants by different factors, i.e. sex, menstrual cycle and inherent pain sensitivities.
Methods
Pain-free, healthy participants between 20 and 40 years of age were recruited for this study. Based on their day post menstruation, each female was assigned to either follicular phase (1-14 days post menstruation) or luteal phase (> 14 days post menstruation). Mechanical pain threshold (MPT), heat pain threshold (HPT) and heat pain sensitivity (HPS) were tested on the volar forearm of participants. Then, an experimental heat pain model7 was used to induce SMH on the volar forearm. The perceived pain during the model was recorded on a numeric rating scale. The spatial extent of SMH was mapped from eight different angles using a 256 mN von Frey filament.
Unpaired t-tests were used to compare the induced area of SMH between females and males, and females in the follicular phase and the luteal phase. Spearman correlation analyses were performed to assess the association between the area of SMH and measurements of pain thresholds and pain sensitivity.
Results
Sixty healthy participants (age: 24.6 ± 2.4 years; 40 females, 20 males) were included in this study. The heat pain model induced a pronounced area of SMH in both females (61.6 ± 19.4 cm2) and males (74.0 ± 25.0 cm2) which tended to be larger in males (t=-1.95, p=0.06). With regard to the female menstrual cycle, the area of SMH did not differ between females in the follicular (57.5 ± 21.9 cm2) compared to the luteal phase (64.2 ± 18.6 cm2, t=-0.97, p=0.34). Neither the MPT (rho=-0.22, p=0.10), the HPT (rho=0.09, p=0.51) nor the perceived pain during the heat pain model (rho=0.21, p=0.10) correlated with the area of SMH. The HPS tended to show a weak correlation with the area of SMH (rho=0.25, p=0.054).
Conclusions
Females tended to develop a smaller area of SMH than men. This could potentially be explained by the significantly smaller body height of female participants (f: 166.2 ± 6.1 cm, m: 179.9 ± 7.2 cm, t=-7.21, p<0.001) and the corresponding smaller forearm surface area.8 Only pain sensitivity to heat tended to correlate with the area of SMH. This finding suggests that only pain assessed using suprathreshold stimuli, but not thresholds, could relate to the susceptibility to develop central sensitization. These results provided only limited support that sex, menstrual cycle of females or individual pain sensitivity influence the development of a more pronounced area of SMH in pain-free individuals. Future studies are needed to characterize factors which explain the variability in experimentally-induced SMH in healthy individuals and might show predictive value for the development of chronic pain.
References
1.Treede, R. D., Meyer, R. A., Raja, S. N. & Campbell, J. N. Peripheral and central mechanisms of cutaneous hyperalgesia. Prog. Neurobiol. 38, 397–421 (1992).
2.Woolf, C. J. Central sensitization: Implications for the diagnosis and treatment of pain. Pain 152, S2–S15 (2011).
3.Holst, H., Arendt-Nielsen, L., Mosbech, H. & Elberling, J. Increased capsaicin-induced secondary hyperalgesia in patients with multiple chemical sensitivity. Clin. J. Pain 27, 156–162 (2011).
4.Cayrol, T. et al. Chronic temporomandibular disorders are associated with higher propensity to develop central sensitization: A case-control study. Pain 164, E251–E258 (2023).
5.Burgmer, M. et al. Cerebral mechanisms of experimental hyperalgesia in fibromyalgia. Eur. J. Pain 16, 636–647 (2012).
6.Morris, V., Cruwys, S. & Kidd, B. Increased capsaicin-induced secondary hyperalgesia as a marker of abnormal sensory activity in patients with fibromyalgia. Neurosci. Lett. 250, 205–207 (1998).
7.Jürgens, T. P., Sawatzki, A., Henrich, F., Magerl, W. & May, A. An improved model of heat-induced hyperalgesia – Repetitive phasic heat pain causing primary hyperalgesia to heat and secondary hyperalgesia to pinprick and light touch. PLoS One 9, (2014).
8.Jensen, M. T. & Petersen, K. L. Gender differences in pain and secondary hyperalgesia after heat/capsaicin sensitization in healthy volunteers. J. Pain 7, 211–217 (2006).
Presenting Author
Florin Allmendinger
Poster Authors
Florin Allmendinger
MSc
Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich
Lead Author
Thomas Egger
MSc
Spinal Cord Injury Centre, Balgrist University Hospital, University of Zurich
Lead Author
Sofia Bösch
MSc
Spinal Cord Injury Centre, Balgrist University Hospital, University of Zurich
Lead Author
Paulina Scheuren
University of British Columbia
Lead Author
Michèle Hubli
Spinal Cord Injury Research Center
Lead Author
Topics
- Mechanisms: Biological-Systems (Physiology/Anatomy)