Development of thermal nociception in rats

Falcon, Michal; Guendellman, Danielia; Stolberg, Alex; Frenk, Hanan; Urca, Gideon

doi:10.1016/0304-3959(96)03070-9

Cited by 59 publications

(32 citation statements)

References 16 publications

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“…A comparative study of human infants and rat pups reported that withdrawal reflex thresholds increased during gestation and with postnatal age, suggesting lower pain thresholds at earlier developmental stages [73]. Multiple other studies have demonstrated that the intensity and duration of pain responses were developmentally regulated [74][75][76][77]. Teng and Abbott [75] found that thresholds for formalin-induced pain increased 2.5-fold from 3 to 15 days of age, and 11-fold from the newborn to the adult rat.…”

Section: Increased Sensitivity To Pain In Neonatesmentioning

confidence: 99%

Can Adverse Neonatal Experiences Alter Brain Development and Subsequent Behavior?

Anand

Scalzo²

2000

Neonatology

525

304

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Self-destructive behavior in current society promotes a search for psychobiological factors underlying this epidemic. Perinatal brain plasticity increases the vulnerability to early adverse experiences, thus leading to abnormal development and behavior. Although several epidemiological investigations have correlated perinatal and neonatal complications with abnormal adult behavior, our understanding of the underlying mechanisms remains rudimentary. Models of early experience, such as repetitive pain, sepsis, or maternal separation in rodents and other species have noted multiple alterations in the adult brain, correlated with specific behavioral phenotypes depending on the timing and nature of the insult. The mechanisms mediating such changes in the neonatal brain have remained largely unexplored. We propose that lack of N-methyl-D-aspartate (NMDA) receptor activity from maternal separation and sensory isolation leads to increased apoptosis in multiple areas of the immature brain. On the other hand, exposure to repetitive pain may cause excessive NMDA/excitatory amino acid activation resulting in excitotoxic damage to developing neurons. These changes promote two distinct behavioral phenotypes characterized by increased anxiety, altered pain sensitivity, stress disorders, hyperactivity/attention deficit disorder, leading to impaired social skills and patterns of self-destructive behavior. The clinical important of these mechanisms lies in the prevention of early insults, effective treatment of neonatal pain and stress, and perhaps the discovery of novel therapeutic approaches that limit neuronal excitotoxicity or apoptosis.

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Section: Increased Sensitivity To Pain In Neonatesmentioning

confidence: 99%

Can Adverse Neonatal Experiences Alter Brain Development and Subsequent Behavior?

Anand

Scalzo²

2000

Neonatology

525

304

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“…The threshold for nociceptive withdrawal reflexes is low in neonates and increases with age, reaching adult values between postnatal day 12 (P12) and P20 (Falcon et al, 1996;Jiang and Gebhart, 1998;Teng and Abbott, 1998;Marsh et al, 1999). Electromyographic measurements similarly reveal lower nociceptive threshold as well as prolonged responses in newborns compared with adults (Fitzgerald and Gibson, 1984;Jiang and Gebhart, 1998).…”

Section: Introductionmentioning

confidence: 99%

Differential Maturation of GABA Action and Anion Reversal Potential in Spinal Lamina I Neurons: Impact of Chloride Extrusion Capacity

Cordero-Erausquin¹,

Coull²,

Boudreau³

et al. 2005

J. Neurosci.

101

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A deficit in inhibition in the spinal dorsal horn has been proposed to be an underlying cause of the exaggerated cutaneous sensory reflexes observed in newborn rats. However, the developmental shift in transmembrane anion gradient, potentially affecting the outcome of GABA A transmission, was shown to be completed within 1 week after birth in the spinal cord, an apparent disparity with the observation that reflex hypersensitivity persists throughout the first 2-3 postnatal weeks.To further investigate this issue, we used several approaches to assess the action of GABA throughout development in spinal lamina I (LI) neurons. GABA induced an entry of extracellular calcium in LI neurons from postnatal day 0 (P0) to P21 rats, which involved T-and N-type voltage-gated calcium channels. Gramicidin perforated-patch recordings revealed that the shift in anion gradient was completed by P7 in LI neurons. However, high chloride pipette recordings demonstrated that these neurons had not reached their adult chloride extrusion capacity by P10 -P11. Simultaneous patch-clamp recordings and calcium imaging revealed that biphasic responses to GABA, consisting of a primary hyperpolarization followed by a rebound depolarization, produced a rise in [Ca 2ϩ ] i . Thus, even if E anion predicts GABA A -induced hyperpolarization from rest, a low chloride extrusion capacity can cause a rebound depolarization and an ensuing rise in [Ca 2ϩ ] i . We demonstrate that GABA action in LI neurons matures throughout the first 3 postnatal weeks, therefore matching the time course of maturation of withdrawal reflexes. Immature spinal GABA signaling may thus contribute to the nociceptive hypersensitivity in infant rats.

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“…In addition, flexor reflex cutaneous receptive fields are larger (4) and less organized (6) than in the adult. Thresholds for withdrawal from heat stimuli are also lower in younger animals (7)(8)(9)(10)(11), and the response to formalin has a 10-fold higher sensitivity in neonatal rats compared with weanlings (12,13). The specific C-fiber irritant, mustard oil, is less effective at producing a nociceptive response in the newborn; however, it gradually increases with postnatal age (14,15).…”

mentioning

confidence: 99%

The postnatal development of spinal sensory processing

Fitzgerald

Jennings

1999

Proc. Natl. Acad. Sci. U.S.A.

166

108

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The mechanisms by which infants and children process pain should be viewed within the context of a developing sensory nervous system. The study of the neurophysiological properties and connectivity of sensory neurons in the developing spinal cord dorsal horn of the intact postnatal rat has shed light on the way in which the newborn central nervous system analyzes cutaneous innocuous and noxious stimuli. The receptive field properties and evoked activity of newborn dorsal horn cells to single repetitive and persistent innocuous and noxious inputs are developmentally regulated and ref lect the maturation of excitatory transmission within the spinal cord. These changes will have an important inf luence on pain processing in the postnatal period.Increasing recognition of the importance of pain in infancy and childhood has focused attention on the basic neurobiology of developing pain pathways. After birth, many regions of the somatosensory nervous system undergo changes in connectivity, leading to transient functional stages before the adult pattern is achieved. Such changes are likely to determine pain and sensory processing at each developmental stage.The aim here is to discuss some of the changing features of sensory connections underlying pain processing in the dorsal horn of the spinal cord over the course of postnatal development. The responses of newborn dorsal horn cells to single repetitive and persistent innocuous and noxious inputs are shown to change over the postnatal period. These are discussed in terms of the maturation of excitatory transmission within the spinal cord and how it may influence pain processing in the newborn.Cutaneous Ref lex Function in the Newborn. Although cutaneous reflexes are not evidence of pain perception as such, they can provide information about the sensitivity and selectivity of the neonatal nervous system to nociceptive stimuli. A feature of the cutaneous flexion reflex in the newborn rat, kitten, and human is that it is exaggerated compared with the adult (1-4). Thresholds to mechanical skin stimulation are lower and the reflex muscle contractions more synchronized and long lasting (5, 6). This feature is particularly marked in the first postnatal week in rats, and then gradually changes until the third postnatal week when a rapid maturation takes place. Repeated low-intensity skin stimulation results in hyperexcitability or sensitization of the reflex with lowered thresholds and generalized movements of all limbs that becomes much less pronounced after 29-to 35-wk gestational age in the human and postnatal day 8 (P8) in the rat (4, 5). In addition, flexor reflex cutaneous receptive fields are larger (4) and less organized (6) than in the adult. Thresholds for withdrawal from heat stimuli are also lower in younger animals (7-11), and the response to formalin has a 10

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Development of thermal nociception in rats

Cited by 59 publications

References 16 publications

Can Adverse Neonatal Experiences Alter Brain Development and Subsequent Behavior?

Can Adverse Neonatal Experiences Alter Brain Development and Subsequent Behavior?

Differential Maturation of GABA Action and Anion Reversal Potential in Spinal Lamina I Neurons: Impact of Chloride Extrusion Capacity

The postnatal development of spinal sensory processing

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