Repetitive noxious stimuli during early development affect acute and long-term mechanical sensitivity in rats

Hoogen, Nynke J. van den; Patijn, Jacob; Tibboel, Dick; Joosten, Elbert A.J.

doi:10.1038/s41390-019-0420-x

Cited by 21 publications

(21 citation statements)

References 36 publications

(63 reference statements)

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“…On the other hand, when we analyzed mechanical hyperalgesia, we observed a decrease in pain sensitivity only in adulthood, for both males and females, between the anoxia and control groups. The present results are supported by studies that evaluated nociceptive responses at adulthood, after neonatal noxious stimuli (Davis & Burman, 2020;Ririe et al, 2003;van den Hoogen et al, 2020). In addition, a study conducted by Davis and Burman (2020) revealed that neonatal pain enhances subsequent fear conditioning in adolescent female rats and creates an age-and sexindependent tactile response.…”

Section: Discussionsupporting

confidence: 82%

Neonatal anoxia increases nociceptive response in rats: Sex differences and lumbar spinal cord and insula alterations

Helou

Martins

Arruda

et al. 2021

Intl J of Devlp Neuroscience

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Neonatal anoxia is a well-known world health problem that results in neurodevelopmental deficits, such as sensory alterations that are observed in patients with cerebral palsy and autism disorder, for which oxygen deprivation is a risk factor. Nociceptive response, as part of the sensory system, has been reported as altered in these patients. To determine whether neonatal oxygen deprivation alters nociceptive sensitivity and promotes medium-and long-term inflammatory feedback in the central nervous system, Wistar rats of around 30 h old were submitted to anoxia (100% nitrogen flux for 25 min) and evaluated on PND23 (postpartum day) and PND90. The nociceptive response was assessed by mechanical, thermal, and tactile tests in the early postnatal and adulthood periods. The lumbar spinal cord (SC, L4-L6) motor neurons (MNs) and the posterior insular cortex neurons were counted and compared with their respective controls after anoxia. In addition, we evaluated the possible effect of anoxia on the expression of astrocytes in the SC at adulthood. The results showed increased nociceptive responses in both males and females submitted to anoxia, although these responses were different according to the nociceptive stimulus. A decrease in MNs in adult anoxiated females and an upregulation of GFAP expression in the SC were observed. In the insular cortex, a decrease in the number of cells of anoxiated males was observed in the neonatal period. Our findings suggest that oxygen-deprived nervous systems in rats may affect their response at the sensorimotor pathways and respective controlling centers with sex differences, which were related to the used stimulus.

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Section: Discussionsupporting

confidence: 82%

Neonatal anoxia increases nociceptive response in rats: Sex differences and lumbar spinal cord and insula alterations

Helou

Martins

Arruda

et al. 2021

Intl J of Devlp Neuroscience

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“…The most commonly used species are rodents; however, there are reports of other species being used. For example, piglets who undergo tail docking (P3 or P63) have longterm peripheral mechanical hyperalgesia (tail stump) (212) and distinctive changes in gene expression up to 16 weeks following the procedure (213).…”

Section: Models To Study the Effects Of Early Life Pain On Pain Models To Study The Effects Of Early Life Pain On Pain Occurring Later Inmentioning

confidence: 99%

Early Neonatal Pain—A Review of Clinical and Experimental Implications on Painful Conditions Later in Life

2020

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Modern health care has brought our society innumerable benefits but has also introduced the experience of pain very early in life. For example, it is now routine care for newborns to receive various injections or have blood drawn within 24 h of life. For infants who are sick or premature, the pain experiences inherent in the required medical care are frequent and often severe, with neonates requiring intensive care admission encountering approximately fourteen painful procedures daily in the hospital. Given that much of the world has seen a steady increase in preterm births for the last several decades, an evergrowing number of babies experience multiple painful events before even leaving the hospital. These noxious events occur during a critical period of neurodevelopment when the nervous system is very vulnerable due to immaturity and neuroplasticity. Here, we provide a narrative review of the literature pertaining to the idea that early life pain has significant long-term effects on neurosensory, cognition, behavior, pain processing, and health outcomes that persist into childhood and even adulthood. We refer to clinical and pre-clinical studies investigating how early life pain impacts acute pain later in life, focusing on animal model correlates that have been used to better understand this relationship. Current knowledge around the proposed underlying mechanisms responsible for the long-lasting consequences of neonatal pain, its neurobiological and behavioral effects, and its influence on later pain states are discussed. We conclude by highlighting that another important consequence of early life pain may be the impact it has on later chronic pain states-an area of research that has received little attention.

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“…This is important as descending serotonergic RVM-spinal dorsal horn have been reported to act in a facilitatory way in neonates ( 26 ). In addition, the anti-nociceptive effect of 5-HT1aR becomes more apparent from postnatal day 4 onwards, and this coincides with progressive increase in acute hypersensitivity with cumulative exposure to repetitive needle pricking ( 14 – 16 , 23 ). 5-HT1aR in neonates inhibit nociceptive signaling through a reduced glutamate release from primary afferent terminals or by increasing the incidence of long-term depression induced inhibition of postsynaptic dorsal horn responses ( 28 , 29 , 31 , 32 ).…”

Section: Discussionmentioning

confidence: 97%

“…A separate litter was left completely undisturbed (UC; n = 10). Rat pups (conditions 1–3) were noxiously stimulated with repetitive needle pricks (NP) four times a day at 09:00 a.m., 10:00 a.m., 11:00 a.m. and 12:00 p.m. from P0 to P7 as previously described ( 13 , 14 ). Each noxious stimulation consisted of a single 2 mm deep needle prick with a 25G needle in the mid-plantar surface of the left hind paw.…”

Section: Methodsmentioning

confidence: 99%

Selective Targeting of Serotonin 5-HT1a and 5-HT3 Receptors Attenuates Acute and Long-Term Hypersensitivity Associated With Neonatal Procedural Pain

et al. 2022

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Neonatal painful procedures causes acute pain and trigger long-term changes in nociceptive processing and anxiety behavior, highlighting the need for adequate analgesia during this critical time. Spinal serotonergic receptors 5-HT1a and 5-HT3 play an important role in modulating incoming nociceptive signals in neonates. The current study aims to attenuate acute and long-term hypersensitivity associated with neonatal procedural pain using ondansetron (a 5-HT3 antagonist) and buspirone (a 5-HT1a agonist) in a well-established rat model of repetitive needle pricking. Sprague-Dawley rat pups of both sexes received ondansetron (3 mg/kg), buspirone (3 mg/kg) or saline prior to repetitive needle pricks into the left hind-paw from postnatal day 0–7. Control animals received tactile stimulation or were left undisturbed. Acute, long-term, and post-operative mechanical sensitivity as well as adult anxiety were assessed. Neonatal 5-HT1a receptor agonism completely reverses acute hypersensitivity from P0-7. The increased duration of postoperative hypersensitivity after re-injury in adulthood is abolished by 5-HT3 receptor antagonism during neonatal repetitive needle pricking, without affecting baseline sensitivity. Moreover, 5-HT1a and 5-HT3 receptor modulation decreases adult state anxiety. Altogether, our data suggests that targeted pharmacological treatment based on the modulation of spinal serotonergic network via the 5-HT1a and 5-HT3 receptors in neonates may be of use in treatment of neonatal procedural pain and its long-term consequences. This may result in a new mechanism-based therapeutic venue in treatment of procedural pain in human neonates.

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Repetitive noxious stimuli during early development affect acute and long-term mechanical sensitivity in rats

Cited by 21 publications

References 36 publications

Neonatal anoxia increases nociceptive response in rats: Sex differences and lumbar spinal cord and insula alterations

Neonatal anoxia increases nociceptive response in rats: Sex differences and lumbar spinal cord and insula alterations

Early Neonatal Pain—A Review of Clinical and Experimental Implications on Painful Conditions Later in Life

Selective Targeting of Serotonin 5-HT1a and 5-HT3 Receptors Attenuates Acute and Long-Term Hypersensitivity Associated With Neonatal Procedural Pain

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