Repeated neonatal needle‐prick stimulation increases inflammatory mechanical hypersensitivity in adult rats

Abstract

Background and aims Newborn infants are vulnerable to procedural stress and pain exposure on the first weeks of life that represents a critical period for the development of nociceptive, sensory, emotional, and social functions. We evaluated the nociceptive behavior of adult male and female rats that were submitted to nociceptive experience in the neonatal period and the maternal behavior in the postnatal period. Methods The animals were submitted to repetitive needle pricking from the second to the fifteenth postnatal day (PND 2–15). Maternal behavior and litter weight were evaluated during this period. Mechanical sensitivity to pain was assessed in offsprings during the adulthood by exposing them to inflammatory stimuli, including formalin test or the Freund's complete adjuvant (CFA) injection followed by the electronic von Frey test at 0, 3, 6 and 24 h later. Results Maternal behavior and litter weight were not altered by pinprick stimuli during PND 2–15. Additionally, pinprick stimulation reduced the paw withdrawal threshold in CFA‐injected animals compared to control. In the formalin test, there was a difference between the genders. Female rats are statically more sensitive to formalin stimulation and showed an increased licking time in both the first and second phases and increased number of flinches in second phase. Conclusions Experiencing early life repetitive pain exposure increased inflammatory pain sensitivity in adult offspring rats and female rats are more sensitive to chemical stimulation. Implications Future investigations of the mechanisms involved in this effect may contribute to the improvement of the understanding of inflammatory pain sensitivity differences.

Neonatal complete Freund's adjuvant-induced inflammation does not induce or alter hyperalgesic priming or alter adult distributions of C-fibre dorsal horn innervation

“…We also found that neonatal CFA had no effect on inflammation-induced changes in mechanical threshold in adulthood. This correlates with Walker et al 55 who found no alterations in adult thresholds after neonatal CFA or carrageenan, but is in contrast to several previous studies, in which neonatal hind paw CFA, 36 , 48 carrageenan, 46 surgical incision, 6 , 56 or repetitive pin-prick 11 caused a greater magnitude of decrease in mechanical threshold and thermal withdrawal latencies upon reinjury compared to control animals that did not experience neonatal injury.…”

Effectiveness of two extended-release buprenorphine formulations during postoperative period in neonatal rats

“…A limitation of this study is that only thermal and not mechanical hypersensitivity was evaluated, even though mechanical hypersensitivity is known to be present in neonatal rats [ 72 , 73 ]. Von Frey monofilament test is commonly used for mechanical hypersensitivity [ 74 ].…”

Predisposition of Neonatal Maternal Separation to Visceral Hypersensitivity via Downregulation of Small-Conductance Calcium-Activated Potassium Channel Subtype 2 (SK2) in Mice

“…Early physical and psychological life stresses can lead to different long-term behavioral and physical alterations by activation of diverse neural networks [ 16 – 18 ], both contributing to changes of neuroendocrine and signal pathways involved in regulating neuroplasticity. In addition, behavioral abnormalities include somatic and visceral hyperalgesia [ 11 , 12 , 44 , 45 ]. Our findings were in line with these studies that mice experiencing MS developed visceral hypersensitivity.…”