Abstract
Noxious stimulation at critical stages of development has long-term consequences on somatosensory processing in later life, but it is not known whether this developmental plasticity is restricted to nociceptive pathways. Here, we investigate the effect of repeated neonatal noxious or innocuous hind paw stimulation on adult spinal dorsal horn cutaneous mechanical sensitivity. Neonatal Sprague-Dawley rats of both sexes received 4 unilateral left hind paw needle pricks (NPs, n = 13) or 4 tactile (cotton swab touch) stimuli, per day (TC, n = 11) for the first 7 days of life. Control pups were left undisturbed (n = 17). When adult (6-8 weeks), lumbar wide-dynamic-range neuron activity in laminae III-V was recorded using in vivo extracellular single-unit electrophysiology. Spike activity evoked by cutaneous dynamic tactile (brush), pinch and punctate (von Frey hair) stimulation, and plantar receptive field areas were recorded, at baseline and 2 and 5 days after left plantar hind paw incision. Baseline brush receptive fields, von Frey hair, and pinch sensitivity were significantly enhanced in adult NP and TC animals compared with undisturbed controls, although effects were greatest in NP rats. After incision, injury sensitivity of adult wide-dynamic-range neurons to both noxious and dynamic tactile hypersensitivity was significantly greater in NP animals compared with TC and undisturbed controls. We conclude that both repeated touch and needle-prick stimulation in the neonatal period can alter adult spinal sensory neuron sensitivity to both innocuous and noxious mechanical stimulation. Thus, spinal sensory circuits underlying touch and pain processing are shaped by a range of early-life somatosensory experiences.
Highlights
Chronic pain affects the daily lives of 1 in 5 adults worldwide and remains undertreated.[14]
A fall in threshold relative to the TC group was observed after needle pricks (NPs) in all time points from P3-7 in the ipsilateral hind paws (Fig. 1B; TC vs NP at P3:11: P, 0.001,13 P, 0.0001,15 P, 0.01; P4:11 P, 0.0001,13 and 15 P, 0.001; P5: 11 P, 0.05,13 and 15 P, 0.01; P6: 11 P, 0.001,13 P, 0.01,15 P, 0.0001; P7:11 P, 0.0001, 13 P, 0.001,15 P, 0.0001, 2-way analysis of variance (ANOVA) with post hoc Bonferroni)
Baseline NP mechanical withdrawal thresholds recovered each day, but by the end of the week, they were significantly lower than TC baseline thresholds (P6 NP 0.95 6 0.11 g vs TC 1.34 6 0.11 g, P, 0.05, 2-way ANOVA with post hoc Bonferroni)
Summary
Chronic pain affects the daily lives of 1 in 5 adults worldwide and remains undertreated.[14] Successful therapeutic solutions for pain are hampered by the diversity in chronic pain mechanisms and individual differences in pain sensitivity.[45] Recent research suggests that early-life exposure to abnormal sensory stimulation is a major determinant for future pain susceptibility. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. A Department of Anaesthesiology and Pain Management, Maastricht University Medical Centre[1], Maastricht, the Netherlands, b Department of Translational Neuroscience, School of Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands, c Intensive Care, Department of Paediatric Surgery, Erasmus MC-Sophia, Rotterdam, the Netherlands, d Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom. Kwok is with the Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
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