Naturally occurring variations in maternal care modulate the effects of repeated neonatal pain on behavioral sensitivity to thermal pain in the adult offspring

Repeated pain during a critical period of development can have long-term behavioral and physiological consequences in both human and animals. We previously showed that rat mothers caring for pups subjected to mild pain in neonatal life increased pup licking and grooming behavior. Therefore, we tested whether naturally occurring variations in maternal behavior would modulate the effects of repeated mild inflammatory pain on behavioral responses to pain and stress in the adult male offspring. Rat pups were either uninjected (UI) or injected twice daily between PND3 and PND14 with either saline (0.9%) or formalin (0.2-0.4%) in the footpad of the hindpaw. Maternal behavior (pup licking and grooming) was recorded under basal conditions and after reunion with the litter post injection to determine maternal phenotype (High, Middle, Low licking). Adult offspring (PND60) were tested for their thermal sensitivity, inflammatory pain responses after formalin injection and neuroendocrine responses to formalin injection. Maternal phenotype significantly altered pain sensitivity after thermal stimulation, but not formalin injection. Offspring from the High licking mothers displayed increased withdrawal latencies compared to offspring from Low mothers, regardless of neonatal treatment. Pain responses after formalin injection were higher in offspring receiving formalin as neonates compared to saline-treated or uninjected rats, demonstrating a long lasting increased sensitivity to inflammatory pain. Neuroendocrine responses to pain stress were not affected by neonatal treatment. These data suggest that changes in maternal behavior can influence some modalities of pain sensitivity and that repeated mild inflammatory pain in neonatal period causes hypersensitivity to formalin in the adult offspring.