Effects of multiple anesthetic exposures on rhesus macaque brain development: a longitudinal structural MRI analysis.

Concerns about the potential neurotoxic effects of anesthetics on developing brain exist. When making clinical decisions, the timing and dosage of anesthetic exposure are critical factors to consider due to their associated risks. In our study, we investigated the impact of repeated anesthetic exposures on the brain development trajectory of a cohort of rhesus monkeys (n = 26) over their first 2 yr of life, utilizing longitudinal magnetic resonance imaging data. We hypothesized that early or high-dose anesthesia exposure could negatively influence structural brain development. By employing the generalized additive mixed model, we traced the longitudinal trajectories of brain volume, cortical thickness, and white matter integrity. The interaction analysis revealed that age and cumulative anesthetic dose were variably linked to white matter integrity but not to morphometric measures. Early high-dose exposure was associated with increased mean, axial, and radial diffusivities across all white matter regions, compared to late-low-dose exposure. Our findings indicate that early or high-dose anesthesia exposure during infancy disrupts structural brain development in rhesus monkeys. Consequently, the timing of elective surgeries and procedures that require anesthesia for children and pregnant women should be strategically planned to account for the cumulative dose of volatile anesthetics, aiming to minimize the potential risks to brain development.

Perioperative Considerations for Patients Exposed to Psychostimulants.

Concerns regarding the perioperative management of acute psychostimulant intoxication have been recognized for decades, but novel and diverse substances in this class continue to be developed. Despite the similarities in mechanisms of action among psychostimulants, each subclass within this broad category has unique receptor specificity and different mechanisms that play a role in patient clinical presentation. These issues present challenges to anesthesia providers when caring for patients with either acute or chronic exposure to psychostimulants during the perioperative period. Challenges result from both physiological and psychological effects that influence the action of the primary anesthetic agent, adjuvant anesthetics, and analgesics used for perioperative management of pain. The epidemiology, pharmacology, and perioperative implications of psychostimulant use are presented for amphetamines and similar acting nonamphetamines, cocaine, and, finally, the mixed-action drugs known as entactogens that share stimulant and psychedelic properties. This information is then used as the foundation for safe and effective perioperative management of patients exposed to psychostimulants.

Risk factors for administration of additional reversal following neuromuscular blockade with rocuronium in children: A retrospective case-control study.

BACKGROUND: The prevalence and risk factors for residual neuromuscular blockade in children remain poorly characterized. We hypothesize that specific patient and anesthetic risk factors may be associated with the administration of additional reversal in children following initial reversal of rocuronium with neostigmine. METHODS: Our electronic health record was queried for patients <18 years of age who received rocuronium and reversal with neostigmine from 2017 through 2020. Patients receiving other nondepolarizing neuromuscular blocking drugs were excluded. The outcome of interest was defined as the administration of additional neostigmine or sugammadex following primary reversal with neostigmine. Time between the last dose of rocuronium and initial dose of neostigmine, and the cumulative dose of rocuronium were dichotomized. These were combined with other covariates including age, weight, sex, racial group, procedure type, ASA physical status, >1 rocuronium dose administered during the procedure, initial neostigmine dose <0.05 mg kg-1 , use of train-of-four monitoring, duration of anesthesia, inpatient or outpatient, emergency case, neuromuscular disease, and extremes of weight, to assess possible associations with the primary outcome. RESULTS: During the study period, 101/6373 (1.58%) patients received rocuronium and additional reversal. Dichotomization of time between last dose of rocuronium and neostigmine yielded <28 min since the last dose of rocuronium and cumulative dose of rocuronium >0.45 mg kg-1 hr-1 . These were associated with the administration of additional reversal with an OR 1.52 (95% CI, 1.08-2.35) and OR 1.71 (95% CI, 1.10-2.67), respectively. Other risk factors included an initial neostigmine dose <0.05 mg kg-1 , OR 4.98 (95% CI, 2.84-6.49), and African American race, OR 1.78 (95% CI, 1.07-2.87). CONCLUSION: Risk factors associated with the administration of additional reversal included time <28 min from the last dose of rocuronium to initial dose of neostigmine, cumulative dose of rocuronium >0.45 mg kg-1 hr-1 , initial neostigmine dose <0.05 mg kg-1 , and African American race.

Assessment of Common Criteria for Awake Extubation in Infants and Young Children.

BACKGROUND: Practice patterns surrounding awake extubation of pediatric surgical patients remain largely undocumented. This study assessed the value of commonly used predictors of fitness for extubation to determine which were most salient in predicting successful extubation following emergence from general anesthesia with a volatile anesthetic in young children. METHODS: This prospective, observational study was performed in 600 children from 0 to 7 yr of age. The presence or absence of nine commonly used extubation criteria in children were recorded at the time of extubation including: facial grimace, eye opening, low end-tidal anesthetic concentration, spontaneous tidal volume greater than 5 ml/kg, conjugate gaze, purposeful movement, movement other than coughing, laryngeal stimulation test, and oxygen saturation. Extubations were graded as Successful, Intervention Required, or Major Intervention Required using a standard set of criteria. The Intervention Required and Major Intervention Required outcomes were combined as a single outcome for analysis of predictors of success. RESULTS: Successful extubation occurred in 92.7% (556 of 600) of cases. Facial grimace odds ratio, 1.93 (95% CI, 1.03 to 3.60; P = 0.039), purposeful movement odds ratio, 2.42 (95% CI, 1.14 to 5.12; P = 0.022), conjugate gaze odds ratio, 2.10 (95% CI, 1.14 to 4.01; P = 0.031), eye opening odds ratio, 4.44 (95% CI, 1.06 to 18.64; P= 0.042), and tidal volume greater than 5 ml/kg odds ratio, 2.66 (95% CI, 1.21 to 5.86; P = 0.015) were univariately associated with the Successful group. A stepwise increase in any one, in any order, of these five predictors being present, from one out of five and up to five out of five yielded an increasing positive predictive value for successful extubation of 88.3% (95% CI, 82.4 to 94.3), 88.4% (95% CI, 83.5 to 93.3), 96.3% (95% CI, 93.4 to 99.2), 97.4% (95% CI, 94.4 to 100), and 100% (95% CI, 90 to 100). CONCLUSIONS: Conjugate gaze, facial grimace, eye opening, purposeful movement, and tidal volume greater than 5 ml/kg were each individually associated with extubation success in pediatric surgical patients after volatile anesthetic. Further, the use of a multifactorial approach using these predictors, may lead to a more rational and robust approach to successful awake extubation.

Incisional Nociceptive Input Impairs Attention-related Behavior and Is Associated with Reduced Neuronal Activity in the Prefrontal Cortex in Rats.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Cognitive capacity may be reduced from inflammation, surgery, anesthesia, and pain. In this study, we hypothesized that incision-induced nociceptive input impairs attentional performance and alters neuronal activity in the prefrontal cortex. METHODS: Attentional performance was measured in rats by using the titration variant of the 5-choice serial reaction time to determine the effect of surgical incision and anesthesia in a visual attention task. Neuronal activity (single spike and local field potentials) was measured in the medial prefrontal cortex in animals during the task. RESULTS: Incision significantly impaired attention postoperatively (area under curve of median cue duration-time 97.2 ± 56.8 [n = 9] vs. anesthesia control 25.5 ± 14.5 s-days [n = 9], P = 0.002; effect size, η = 0.456). Morphine (1 mg/kg) reduced impairment after incision (area under curve of median cue duration-time 31.6 ± 36.7 [n = 11] vs. saline 110 ± 64.7 s-days [n = 10], P < 0.001; η = 0.378). Incision also decreased cell activity (n = 24; 1.48 ± 0.58 vs. control, 2.93 ± 2.02 bursts/min; P = 0.002; η = 0.098) and local field potentials (n = 28; η = 0.111) in the medial prefrontal cortex. CONCLUSIONS: These results show that acute postoperative nociceptive input from incision reduces attention-related task performance and decreases neuronal activity in the medial prefrontal cortex. Decreased neuronal activity suggests nociceptive input is more than just a distraction because neuronal activity increases during audiovisual distraction with similar behavioral impairment. This suggests that nociceptive input and the medial prefrontal cortex may contribute to attentional impairment and mild cognitive dysfunction postoperatively. In this regard, pain may affect postoperative recovery and return to normal activities through attentional impairment by contributing to lapses in concentration for routine and complex tasks.

An initial experience with an Extraluminal EZ-Blocker® : A new alternative for 1-lung ventilation in pediatric patients.

BACKGROUND: The need for 1-lung ventilation in school age, pediatric patients is uncommon and as a result there are relatively few devices available to facilitate lung isolation in this population. Furthermore, little is known about the efficacy and techniques of placement of the currently available devices. One of the newest devices available that may be appropriate in this age group is the EZ-Blocker. AIMS: We aimed to examine our initial experience with the EZ-Blocker to evaluate the performance of this device with respect to potential improvements in technique and patient selection going forward. METHODS: We performed a retrospective chart review of all pediatric patients who underwent 1-lung ventilation with an EZ-Blocker since the blocker became available at our institution. We recorded demographics, details of placement, intraoperative course, number of repositions, and any postoperative morbidity related to blocker placement or 1-lung ventilation. RESULTS: We were able to correctly place the EZ-Blocker and achieve lung isolation in 8 of 11 patients. There was a single episode of repositioning required during 1-lung ventilation with an EZ-Blocker. CONCLUSION: The EZ-Blocker was successful in providing lung isolation for a majority of our school age patients. Size constraints in children <6 years of age, excessive secretions, and distortions of tracheal anatomy seemed to be the greatest hindrances to successful placement and positioning of the device. Once correctly positioned, however, the EZ-Blocker may be more stable than the Arndt endobronchial blocker.

Post-discharge hyperpolarization is an endogenous modulatory factor limiting input from fast-conducting nociceptors (AHTMRs).

Peripheral somatosensory neurons are frequently exposed to mechanical forces. Strong stimuli result in neuronal activation of high-threshold mechanosensory afferent neurons, even in the absence of tissue damage. Among these neurons, fast-conducting nociceptors (A-fiber high-threshold mechanoreceptors (AHTMRs)) are normally resistant to sustained activation, transiently encoding the mechanical stimulus intensity but not its full duration. This rapidly adapting response seems to depend on changes in the electrical excitability of the membrane of these afferent neurons during sustained stimulation, a restraint mechanism that disappears following sensitization. Here, we examine the mechanism by which strong peripheral activation of mechanoreceptors elicits this control process in the absence of tissue injury and temporally silences afferent neurons despite ongoing stimulation. To study this, mechanoreceptors in Sprague-Dawley rats were accessed at the soma in the dorsal root ganglia from T11 and L4/L5. Neuronal classification was performed using receptive field characteristics and passive and active electrical properties. Sustained mechanical nociceptive stimulation in the absence of tissue damage of AHTMRs induces a rapid membrane hyperpolarization and a period of reduced responsiveness to the stimuli. Moreover, this phenomenon appears to be unique to this subset of afferent neurons and is absent in slow-conducting C-mechanonociceptors (C-fiber high-threshold mechanoreceptors) and rapidly adapting fast-conducting low-threshold mechanoreceptors. Furthermore, this mechanism for rapid adaptation and reducing ongoing input is ablated by repeated strong stimuli and in sensitized AHTMRs after chronic neuropathic injury. Further studies to understand the underling molecular mechanisms behind this phenomenon and their modulation during the development of pathological conditions may provide new targets to control nociceptive hyperexcitability and chronic pain.

Assessment of Behavioral Disruption in Rats with Abdominal Inflammation Using Visual Cue Titration and the Five-choice Serial-reaction Time Task.

BACKGROUND: Both acute and chronic pain result in a number of behavioral symptoms in patients, including cognitive effects such as decreased attention and working memory. Intraperitoneal administration of dilute lactic acid in rodents has been used to induce abdominal inflammation and produce effects in behavioral assays of both sensory-discriminative and affective pain modalities. METHODS: Intraperitoneal injection of dilute lactic acid was used to study the impact of abdominal inflammation on an operant task requiring sustained visual attention in rats (N = 7 to 15/group) that adapts dynamically to performance ability. The effects of ketoprofen and morphine on lactic acid-induced impairment were compared with those on the disruptive effects of scopolamine. RESULTS: Lactic acid impaired performance in a concentration-dependent manner, increasing the duration of cue presentation required to maintain optimal performance from 0.5 ± 0.2 s (mean ± SD) to 17.2 ± 11.4 s after the administration of 1.8% (v/v) (N = 13). The latency to emit correct responses and to retrieve the food reward were both increased by lactic acid. All effects of lactic acid injection were reversed by both ketoprofen and morphine in a dose-dependent manner. Scopolamine, however, produced dose-dependent, nonpain-related disruption in sustained attention that was not altered by either ketoprofen or morphine. CONCLUSIONS: These data demonstrate that abdominal inflammation induced by lactic acid produces robust disruption in a visual attention-based operant task and that this disruption is reversed by analgesics. Future studies will focus on pain-related circuitry and its impact on both limbic forebrain and frontal cortical mechanisms.

Mechanical sensibility of nociceptive and non-nociceptive fast-conducting afferents is modulated by skin temperature.

The ability to distinguish mechanical from thermal input is a critical component of peripheral somatosensory function. Polymodal C fibers respond to both stimuli. However, mechanosensitive, modality-specific fast-conducting tactile and nociceptor afferents theoretically carry information only about mechanical forces independent of the thermal environment. We hypothesize that the thermal environment can nonetheless modulate mechanical force sensibility in fibers that do not respond directly to change in temperature. To study this, fast-conducting mechanosensitive peripheral sensory fibers in male Sprague-Dawley rats were accessed at the soma in the dorsal root ganglia from T11 or L4/L5. Neuronal identification was performed using receptive field characteristics and passive and active electrical properties. Neurons responded to mechanical stimuli but failed to generate action potentials in response to changes in temperature alone, except for the tactile mechanical and cold sensitive neurons. Heat and cold ramps were utilized to determine temperature-induced modulation of response to mechanical stimuli. Mechanically evoked electrical activity in non-nociceptive, low-threshold mechanoreceptors (tactile afferents) decreased in response to changes in temperature while mechanically induced activity was increased in nociceptive, fast-conducting, high-threshold mechanoreceptors in response to the same changes in temperature. These data suggest that mechanical activation does not occur in isolation but rather that temperature changes appear to alter mechanical afferent activity and input to the central nervous system in a dynamic fashion. Further studies to understand the psychophysiological implications of thermal modulation of fast-conducting mechanical input to the spinal cord will provide greater insight into the implications of these findings.

Nerve injury induces a new profile of tactile and mechanical nociceptor input from undamaged peripheral afferents.

Chronic pain after nerve injury is often accompanied by hypersensitivity to mechanical stimuli, yet whether this reflects altered input, altered processing, or both remains unclear. Spinal nerve ligation or transection results in hypersensitivity to mechanical stimuli in skin innervated by adjacent dorsal root ganglia, but no previous study has quantified the changes in receptive field properties of these neurons in vivo. To address this, we recorded intracellularly from L4 dorsal root ganglion neurons of anesthetized young adult rats, 1 wk after L5 partial spinal nerve ligation (pSNL) or sham surgery. One week after pSNL, hindpaw mechanical withdrawal threshold in awake, freely behaving animals was decreased in the L4 distribution on the nerve-injured side compared with sham controls. Electrophysiology revealed that high-threshold mechanoreceptive cells of A-fiber conduction velocity in L4 were sensitized, with a seven-fold reduction in mechanical threshold, a seven-fold increase in receptive field area, and doubling of maximum instantaneous frequency in response to peripheral stimuli, accompanied by reductions in after-hyperpolarization amplitude and duration. Only a reduction in mechanical threshold (minimum von Frey hair producing neuronal activity) was observed in C-fiber conduction velocity high-threshold mechanoreceptive cells. In contrast, low-threshold mechanoreceptive cells were desensitized, with a 13-fold increase in mechanical threshold, a 60% reduction in receptive field area, and a 40% reduction in instantaneous frequency to stimulation. No spontaneous activity was observed in L4 ganglia, and the likelihood of recording from neurons without a mechanical receptive field was increased after pSNL. These data suggest massively altered input from undamaged sensory afferents innervating areas of hypersensitivity after nerve injury, with reduced tactile and increased nociceptive afferent response. These findings differ importantly from previous preclinical studies, but are consistent with clinical findings in most patients with chronic neuropathic pain.

Skin incision-induced receptive field responses of mechanosensitive peripheral neurons are developmentally regulated in the rat.

Maturation of the nervous system results in changes in both central and peripheral processing. To better understand responses to injury in the young, developmental differences in the acute response to incision were investigated in both tactile and nociceptive myelinated peripheral mechanosensitive afferent neurons in vivo. Neuronal intrasomal recordings were performed in juvenile and infant rats in 34 L5 dorsal root ganglia, and each neuron was phenotypically defined. Neurons had a mechanosensitive receptive field in the glabrous skin on the plantar surface of the hind paw, which was characterized at baseline and for up to 45 min after incision. Fundamental maturational differences in the effect of incision were clear: in high-threshold nociceptive mechanoreceptors, the mechanical threshold decreased immediately and the receptive field size increased rapidly in juvenile rats but not in infant rats. Additionally, a divergence in changes in the instantaneous response frequency of tactile afferents occurred between the two ages. These differences may help explain maturational differences in responses to peripheral injury and suggest that differences in central nervous system responses may be partially mitigated by spatially confined and frequency-dependent differences resulting from tactile and nociceptive mechanosensitive input.

Time-dependent perioperative anesthetic management and outcomes of the first 100 consecutive cases of spring-assisted surgery for sagittal craniosynostosis.

BACKGROUND: The anesthetic risks and outcomes of the first 100 consecutive spring-assisted surgeries (SAS) for cranial expansion from a single institution are reported. The effect of number of procedures was also tested on hematocrit postoperative day 1 (POD1), anesthesia time, and surgery time of the first procedure. METHODS: The records of 100 consecutive patients undergoing SAS were reviewed. Anesthesia management and related complications are presented. Time series linear regression analysis was performed on hematocrit POD1, anesthesia time, and surgery time of the first procedure. RESULTS: The average age of the first insertion procedure was 4.4 and 9.0 months for the second removal procedure. Two patients were inadvertently extubated during positioning. Thirty-eight children had a decrease in blood pressure >20% from baseline. No child was admitted to the intensive care unit. No patient received any blood or blood product transfusion. Anesthesia time, surgery time, and hematocrit POD1 were correlated with procedure number or experience. CONCLUSIONS: Changes in anesthetic management resulted from changing the procedure. The reduction in volume resuscitation reduces the need for invasive monitoring. Facility and comfort with the surgical procedure increase with time and number of procedures performed. This experience further reduces blood loss and risk of transfusion.

A Painful Beginning: Early Life Surgery Produces Long-Term Behavioral Disruption in the Rat.

Early life surgery produces peripheral nociceptive activation, inflammation, and stress. Early life nociceptive input and inflammation have been shown to produce long-term processing changes that are not restricted to the dermatome of injury. Additionally stress has shown long-term effects on anxiety, depression, learning, and maladaptive behaviors including substance abuse disorder and we hypothesized that early life surgery would have long-term effects on theses complex behaviors in later life. In this study surgery in the rat hindpaw was performed to determine if there are long-term effects on anxiety, depression, audiovisual attention, and opioid reward behaviors. Male animals received paw incision surgery and anesthesia or anesthesia alone (sham) at postnatal day 6. At 10 weeks after surgery, open field center zone entries were decreased, a measure of anxiety (n = 20) (P = 0.03) (effect size, Cohen's d = 0.80). No difference was found in the tail suspension test as a measure of depression. At 16-20 weeks, attentional performance in an operant task was similar between groups at baseline and decreased with audiovisual distraction in both groups (P < 0.001) (effect size, η2 = 0.25), but distraction revealed a persistent impairment in performance in the surgery group (n = 8) (P = 0.04) (effect size, η2 = 0.13). Opioid reward was measured using heroin self-administration at 16-24 weeks. Heroin intake increased over time in both groups during 24-h free access (P < 0.001), but was greater in the surgery group (P = 0.045), with a significant interaction between time and treatment (P < 0.001) (effect size, Cohen f 2 = 0.36). These results demonstrate long-term disruptions in complex behaviors from surgical incision under anesthesia. Future studies to explore sex differences in early life surgery and the attendant peripheral neuronal input, stress, and inflammation will be valuable to understand emerging learning deficits, anxiety, attentional dysfunction, and opioid reward and their mechanisms. This will be valuable to develop optimal approaches to mitigate the long-term effects of surgery in early life.

Differing neurophysiologic mechanosensory input from glabrous and hairy skin in juvenile rats.

Sensory afferents in skin encode and convey thermal and mechanical conditions, including those that threaten tissue damage. A small proportion of skin, the glabrous skin of the distal extremities, is specialized to explore the environment in fine detail. Aside from increased innervation density, little is known regarding properties of mechanosensory afferents to glabrous skin in younger animals that explain the exquisite precision and high contrast in rapidly sampling physical structures, including those that threaten injury. To assess this, we obtained intact neuronal intracellular recordings in vivo from 115 mechanosensitive afferent neurons from lumbar and thoracic dorsal root ganglia in juvenile rats. Two characteristics were unique to glabrous skin: a threefold higher proportion of fast-conducting to slow-conducting afferents that were high-threshold mechanosensitive nociceptors compared with hairy skin and a twofold faster conduction velocity of fast-conducting nociceptors compared with hairy skin. Additionally differences were found in mechanical thresholds between glabrous skin and hairy skin for each fiber type. These differences reflect and help explain the rapid response of skin specialized to explore the physical environment. Additionally, these results highlight potential limitations of using passive electrical properties and conduction velocity alone to characterize primary afferents without knowledge of the skin type they innervated.

Recovery from nerve injury induced behavioral hypersensitivity in rats parallels resolution of abnormal primary sensory afferent signaling.

Pain and hypersensitivity months after peripheral injury reflect abnormal input from peripheral afferents likely in conjunction with central sensitization. We hypothesize that peripheral changes occur in defined sensory afferents and resolve as behavioral response to injury resolves. Male Sprague-Dawley rats underwent sham or partial L5 spinal nerve ligation, and paw withdrawal threshold (PWT) was sequentially measured during recovery. At 2, 4, 8, and 12 weeks after injury, randomized animals underwent electrophysiologic assessment of L4 fast-conducting high- and low-threshold mechanoreceptors, and individual neuronal mechanical thresholds (MTs) were contrasted with PWTs in the same animals. Paw withdrawal thresholds decreased after injury and resolved over time (P < 0.001). Similarly, MTs of fast-conducting high-threshold mechanoreceptors decreased after injury and resolved over time (P < 0.001). By contrast, MTs of low-threshold mechanoreceptors increased after injury and resolved over time (P < 0.001). Distributions of recordings from each afferent subtype were perturbed after injury, and this too resolved over time. After resolution of behavioral changes, several electrical abnormalities persisted in both neuronal subtypes. These data extend previous findings that mechanically sensitive nociceptors are sensitized, whereas tactile, largely Aß afferents are desensitized after nerve injury by showing that the time course of resolution of these changes mirrors that of behavioral hypersensitivity in a surgical injury including neural damage. These data support a role of abnormal peripheral input, from both nociceptor and tactile afferents, during recovery from peripheral injury and underscore the potential importance of both classes of afferents as potential targets for pain treatment.

Nociceptive input after peripheral nerve injury results in cognitive impairment and alterations in primary afferent physiology in rats.

Pain alters cognitive performance through centrally mediated effects in the brain. In this study, we hypothesized that persistent activation of peripheral nociceptors after injury would lead to the development of a chronic pain state that impairs attention-related behavior and results in changes in peripheral neuron phenotypes. Attentional performance was measured in rats using the 5-choice serial reaction time titration variant to determine the initial impact of partial L5 spinal nerve ligation and the effect of persistent nociceptor activation on the resolution of injury. The changes in peripheral neuronal sensibilities and phenotypes were determined in sensory afferents using electrophysiologic signatures and receptive field properties from dorsal root ganglion recordings. Partial spinal nerve injury impaired attentional performance, and this was further impaired in a graded fashion by nociceptive input through an engineered surface. Impairment in attention persisted for only up to 4 days initially, followed by a second phase 7 to 10 weeks after injury in animals exposed to nociceptive input. In animals with prolonged impairment in behavior, the mechanonociceptors displayed a persistent hypersensitivity marked by decreased threshold, increased activity to a given stimulus, and spontaneous activity. Nerve injury disrupts attentional performance acutely and is worsened with peripheral mechanonociceptor activation. Acute impairment resolves, but persistent nociceptive activation produces re-emergence of impairment in the attention-related task associated with electrophysiological abnormalities in peripheral nociceptors. This is consistent with the development of a chronic pain state marked by cognitive impairment and related to persistently abnormal peripheral input.

Comparison of the immediate effects of surgical incision on dorsal horn neuronal receptive field size and responses during postnatal development.

BACKGROUND: Pain behavior in response to skin incision is developmentally regulated, but little is known about the underlying neuronal mechanisms. The authors hypothesize that the spatial activation and intensity of dorsal horn neuron responses to skin incision differ in immature and adult spinal cord. METHODS: Single wide-dynamic-range dorsal horn cell spike activity was recorded for a minimum of 2 h from anesthetized rat pups aged 7 and 28 days. Cutaneous pinch and brush receptive fields were mapped and von Frey hair thresholds were determined on the plantar hind paw before and 1 h after a skin incision was made. RESULTS: Baseline receptive field areas for brush and pinch were larger and von Frey thresholds lower in the younger animals. One hour after the incision, brush and pinch receptive field area, spontaneous firing, and evoked spike activity had significantly increased in the 7-day-old animals but not in the 28-day-old animals. Von Frey hair thresholds decreased at both ages. CONCLUSIONS: Continuous recording from single dorsal horn cells both before and after injury shows that sensitization of receptive fields and of background and afferent-evoked spike activity at 1 h is greater in younger animals. This difference is not reflected in von Frey mechanical thresholds. These results highlight the importance of studying the effects of injury on sensory neuron physiology. Injury in young animals induces a marked and rapid increase in afferent-evoked activity in second-order sensory neurons, which may be important when considering long-term effects and analgesic interventions.