Noxious Stimuli Research Articles

Incoherence in the Brain Death Guideline Regarding Brain Blood Flow Testing: Lessons from the Much-Publicized Case of Zack Dunlap

At age 21, following a severe traumatic brain injury, Zack Dunlap was declared brain-dead according to the American Academy of Neurology guideline (Guideline) when he met the clinical criteria of brain death (minus apnea testing because of bradycardia) with technetium-99m diethylene-triamine-pentaacetate scintigraphy reported as showing no intracranial blood flow. His parents agreed to organ donation. During preparations for organ donation, Zack manifested a purposeful movement in response to a noxious stimulus made by his cousin. Following subsequent neurological recovery, he has returned to a normal life, holding steady employment and raising a family. During an interview, he reported that while in coma, he heard a doctor say that he was brain-dead and felt angry about it. His experience fits the phenomenon of cognitive-motor dissociation. Recently, Zack's medical records were made available to the first author. A critical review of the records uncovered a problem inherent in the logic of the Guideline algorithm regarding brain blood flow scintigraphy. This article discusses the lessons drawn from Zack's case, namely, that both the aforementioned problem and the occurrence of cognitive-motor dissociation in patients deemed to be brain-dead can pose a significant risk of a false-positive declaration of death.

Eyes on Newborns: How NICU Staff's Attention and Emotions Shape Neonatal Pain Assessment.

Assessing pain in neonates is crucial for their management but is inherently subjective. This study investigated the effects of visual attention, gaze patterns, and empathic responses of neonatal healthcare professionals on their assessments of neonatal pain. Conducted at the Department of Neonatology, University Medical Center Hamburg-Eppendorf, we employed eye-tracking to monitor staff's responses to videos depicting neonates experiencing non-noxious thermal, brief noxious, and prolonged noxious stimuli. Videos were presented in two formats: full body view, providing contextual information, and face-only view, lacking contextual details. Pain assessments were measured using a Faces Pain Rating Scale (FPRS), exploring the impacts of contextual cues, professional experience, and job roles. The study found brief and prolonged noxious stimuli eliciting significantly higher FPRS scores compared to non-painful stimuli, with the full body view resulting in higher pain ratings than the face-only view. The mouth region attracted focused attention. Nurses generally reported higher pain scores and exhibited larger pupil diameters compared to physicians, suggesting a stronger empathic response. This research highlights the essential role of visual cues and empathic responses in neonatal pain assessment, demonstrating how professional roles and stimulus presentation format impact evaluations, and underlining the need for standardised protocols to improve neonatal pain management accuracy. The study emphasises the importance of visual cues and empathy in neonatal pain assessment, highlighting the roles of healthcare professionals and stimulus presentation formats. It addresses challenges in understanding neonatal pain, advocating for standardised protocols. Using eye-tracking technology, the research explores how professionals' visual attention and empathy affect pain evaluations, suggesting more objective assessment methods.

Analgesic efficacy of hydromorphone in American alligators (Alligator mississippiensis)

BackgroundAmerican alligators (Alligator mississippiensis) are maintained in zoos, aquaria, and farms for educational, research, and production purposes. The standard of veterinary medical care and welfare for captive reptiles requires managing pain and discomfort under conditions deemed painful in mammals. While analgesic efficacy and pharmacokinetic data for several reptile species are published, data with respect to analgesic efficacy in crocodilians are clearly lacking.ObjectiveThe objective of this study was to determine the analgesic efficacy of hydromorphone in alligators.MethodsFemale American alligators (N = 9; 57 months of age) were exposed to mechanical noxious stimuli at multiple anatomic sites using von Frey filaments ranging in size from 1.65 to 6.65 grams-force, and their behavioral reactions recorded. In order to evaluate analgesic efficacy, hydromorphone (0.5 mg/kg SC) was administered in the axillary region to the same alligators and the mechanical noxious stimuli were repeated and behaviors recorded.ResultsAdministration of hydromorphone contributed to a range from 62 to 92% reduced avoidance reactions to mechanical noxious stimuli for two anatomic sites (i.e., naris and lateral mandible, respectively).ConclusionAlligators did not appear to experience clinically relevant respiratory depression, hypothermia, or other adverse reactions. Therefore, hydromorphone shows promise as an analgesic option to be administered under painful conditions in American alligators.

Comparison of Perioperative Analgesic Efficacy of Lidocaine Intratesticular Block and Spermatic Cord Instillation in Feline Castration

Intratesticular block is an effective local anesthetic technique for castration; however, its use may be limited in cases of testicular masses or infections. Instillation is a simple technique used in several procedures, though studies investigating its application in feline castration remain scarce. Therefore, this study aimed to compare the perioperative analgesic efficacy of lidocaine intratesticular block and spermatic cord instillation in feline castration. Forty-five male cats were randomly divided into three groups: the intratesticular block group (IT), the spermatic cord instillation group (S), and the control group (C). All cats were anesthetized using the same protocol and both techniques were performed based on group assignments. Lidocaine (2 mg/kg) was administrated according to the designated route, while 0.9% normal saline was used for the alternative route and in the C group. Intraoperative parameters were recorded, showing that noninvasive blood pressure in the IT and S groups was significantly lower than in the C group. Although both lidocaine intratesticular block and spermatic cord instillation effectively reduce surgical noxious stimulation, intratesticular block is recommended as it provides more stable intraoperative vital signs and less postoperative pain. Therefore, spermatic cord instillation can be considered as an optional technique for managing pain in feline castration.

Brain under surgical anesthesia: focus on nociception and attention network.

Surgery endangers the integrity of the body through a continuous stream of noxious stimuli. General anesthesia helps patients cope with the surgery situation. In the first part of our literature review, we present our new knowledge about nociception as described by Sherrington. Anesthesiology researchers have discovered the common mechanism of action of various anesthetics for loss of consciousness (LOC). We review the neural correlates of anesthesia. Maintaining the unconscious state created by anesthetics during surgery is only possible by continuously counteracting nociception. Finally, we present the role of the opioid receptor system in antinociception. Understanding all these processes can help expand our knowledge about nociception, pain and formation of consciousness.

Direct evidence of fetal responses to noxious stimulations: A systematic review of physiological and behavioral reactions.

Fetal pain is usually debated using data extrapolated from physiology and anatomy; whereas direct observation of fetal pain reactions is only marginally used. We present the first systematic review to carefully analyse this direct evidence. Our objective was to summarize the scientific literature based on the direct observation of fetal responses to noxious stimulation. We retrieved 17 clinical studies focused on the direct observation of fetal responses to noxious stimulation. This systematic review suggests that direct trials of fetal responses to acute pain/stress caused by tissue injury are scarce, but nonetheless informative for therapeutic interventions using fetal surgery or fetal invasive procedures. The current evidence indicates that responses to fetal pain develop from mid-gestation onward, but further high-quality research is needed to confirm these findings and guide clinical practice.

Differential Neuronal Activation of Nociceptive Pathways in Neuropathic Pain After Spinal Cord Injury

Neuropathic pain, a prevalent complication following spinal cord injury (SCI), severely impairs the life quality of patients. No ideal treatment exists due to incomplete knowledge on underlying neural processes. To explore the SCI-induced effect on nociceptive circuits, the protein expression of c-Fos was analyzed as an indicator of neuronal activation in a rat contusion model exhibiting below-level pain. Additional stimuli were delivered to mimic the different peripheral sensory inputs in daily life. Following noxious rather than innocuous or no stimulation, a greater number of spinal dorsal horn (DH) neurons were activated after SCI, mainly in the deep DH. SCI facilitated the activation of excitatory but not inhibitory DH neurons. Moreover, excitatory interneurons expressing protein kinase C gamma (PKCγ) in laminae II–III, which are known to play a role in mechanical allodynia after peripheral nerve injury, responded in larger amounts to both innocuous and noxious stimulation following SCI. Accordingly, more spinal projection neurons in lamina I were activated. Within supraspinal nuclei processing pain, differentially enhanced activation in response to noxious stimulation was detected after SCI, with a significant increase in the locus coeruleus and medial thalamus, a slight increase in the periaqueductal gray and dorsal raphe, and no change in the lateral parabrachial nucleus or primary sensory cortex. These findings indicated differential hyperexcitability along the sensory neuroaxis following SCI, with a particular emphasis on the involvement of specific neuron subtypes, such as spinal PKCγ interneurons and locus coeruleus noradrenergic neurons, which may serve as crucial targets for potential therapies.Graphical Rats exhibiting pain like behavior after spinal cord injury showed increased engagement of specific subtypes of spinal excitatory neurons and enhanced activity in supraspinal nuclei. The figure was created using Figdraw 2.0.

Lipid nanoparticle delivery of siRNA to dorsal root ganglion neurons to treat pain.

Sensory neurons within the dorsal root ganglion (DRG) are the primary trigger of pain, relaying activity about noxious stimuli from the periphery to the central nervous system; however, targeting DRG neurons for pain management has remained a clinical challenge. Here, we demonstrate the use of lipid nanoparticles (LNPs) for effective intrathecal delivery of small interfering RNA (siRNA) to DRG neurons, achieving potent silencing of the transient receptor potential vanilloid 1 (TRPV1) ion channel that is predominantly expressed in nociceptor sensory neurons. This leads to a reversible interruption of heat-, capsaicin-, and inflammation-induced nociceptive conduction, as observed by behavioral outputs. Our work provides a proof-of-concept for intrathecal siRNA therapy as a novel and selective analgesic modality.

Neuron Modulation by Synergetic Management of Redox Status and Oxidative Stress.

The transient receptor potential (TRP) channel is a key sensor for diverse cellular stimuli, regulating the excitability of primary nociceptive neurons. Sensitization of the TRP channel can heighten pain sensitivity to innocuous or mildly noxious stimuli. Here, reversible modulation of TRP channels is achieved by controlling both the light-induced photoelectrochemical reaction to induce neuronal depolarization, and antioxidants for neuronal protection. It is based on a hybrid nanosystem, CZPN, created by coating CeO2 nanocrystals with the metalloporphyrin ZnTPyP. Light irradiation triggers an electrochemical response, with efficient electron injection from ZnTPyP to CeO2, converting Ce4+ into Ce3+ as antioxidants. Meanwhile, the charge migrates from surrounding O2 molecules to the hole-injected ZnTPyP*, giving rise to reactive oxygen species (ROS). This change in the redox environment sensitizes TRP channels, eliciting action potentials in primary rat neurons, and is partially blocked by pretreatment with capsazepine. The resulting CeO2-x, with a high Ce3+/Ce4+ ratio, can scavenge excessive ROS to prevent oxidative damage. The light-induced pain behaviors in mice pre-injected with CZPN are further confirmed. This work suggests a safe, effective, and universal approach to photoelectrochemical processes for modulation and research of the peripheral nervous system.

The involvement of orexin-1 receptors in modulation of feeding and anxiety-like behavior in rats with complete Freund's adjuvant-induced temporomandibular joint disorder.

Orexin-A (OXA), a neuropeptide produced in the hypothalamus, is recognized for its role in modulating orofacial nociception and regulating feeding behaviors, as well as its impact on psychophysiological responses. This study investigated the role of orexin-1 receptors (OX1R) in modulating nociceptive behaviors induced by noxious stimulation of the temporomandibular joint (TMJ) and the associated changes in mood and feeding behaviors in rats with complete Freund's adjuvant (CFA)-induced temporomandibular disorders (TMDs). Bilateral cannulation of the lateral ventricles was performed in rats. To induce nociception, CFA was injected unilaterally into the left TMJ of the rats. Nociceptive behaviors were assessed using the hot plate and tail flick tests, while anxiety-like behavior and food intake were evaluated using an elevated plus maze (EPM) and a food preference device, respectively. The results demonstrated a significant increase in nociceptive scores and anxiety-like behaviors, along with reductions in water and food consumption following CFA injection. However, post-treatment with OXA at concentrations of 50 and 100pM/rat significantly decreased thermal nociceptive scores, alleviated anxiety-like behavior, and increased water and food intake. These beneficial effects were reversed when OXA was co-administered with SB-334867 (40nM/rat), an OX1R antagonist. Collectively, our findings suggest that OX1R signaling plays a role in the modulation of anxiety-like behavior and abnormalities in food intake in CFA-treated rats. Understanding the involvement of OXA and its receptors in CFA-induced TMJ nociception and behavioral changes may pave the way for potential therapeutic interventions targeting OX1R signaling in the management of TMD-associated symptoms.

Increases in mean arterial blood pressure during electrical stimulation are unreliable indicators of anesthetic depth measured with electroencephalogram in dogs anesthetized with sevoflurane.

To evaluate the sparing effects of fentanyl and maropitant on sevoflurane minimum alveolar concentrations that block autonomic responses (MACBAR) and the hemodynamic and electroencephalographic responses to noxious stimuli in dogs. The sevoflurane MACBAR was determined in 5 healthy male Beagles with or without continuous infusions of fentanyl and maropitant. Then, intermittent noxious stimulation was applied at 1.3, 1.0, and 0.7 MACBAR. Heart rate (HR), mean arterial pressure (MAP), and Patient State Index (PSI) were measured for 6 minutes before and during 6 minutes of stimulation and analyzed with generalized linear mixed-effects models. Patient State Index occurrences above 50 during stimulation were noted. The effective dose for burst suppression was determined. The baseline MACBAR was 2.26% (1.34, 3.19). No MACBAR-sparing effect of fentanyl and maropitant was observed. At 1.3 MACBAR, MAP, HR, and PSI were 50 (41, 91) mm Hg, 90 (64, 112) beats/min, and 2 (0, 44). Mean arterial pressure and PSI increased, but not HR, with lower MACBAR multiples (P < .001). Noxious stimulation did not alter HR or PSI but elevated MAP. No PSI above 50 occurred at 1.3 MACBAR; however, 2 and 3 dogs showed brief PSI increases at 1.0 and 0.7 MACBAR. The effective dose for burst suppression was 3.15% (2.75, 3.75). Fentanyl and maropitant showed no MACBAR-sparing effect. At higher sevoflurane concentrations, noxious stimuli triggered an autonomic response; however, burst suppression was observed in the electroencephalogram. Variations in HR and MAP are unreliable indicators of anesthetic depth measured by electroencephalogram.

Mechanisms of increased pain discrimination by contingent reinforcement: a perceptual decision-making and instrumental learning account.

Recent evidence highlights that monetary rewards can increase the precision at which healthy human volunteers can detect small changes in the intensity of thermal noxious stimuli, contradicting the idea that rewards exert a broad inhibiting influence on pain perception. This effect was stronger with contingent rewards compared with noncontingent rewards, suggesting a successful learning process. In the present study, we implemented a model comparison approach that aimed to improve our understanding of the mechanisms that underlie thermal noxious discrimination in humans. In a between-subject design, 54 healthy human volunteers took part in a pain discrimination task with monetary rewards either contingent or noncontingent on successful discrimination of small changes in the intensity painful heat stimulation. We used models from 2 traditions in decision-making research, perceptual decision-making, and instrumental learning. Replicating the previous findings, only rewards contingent on behavior enhanced pain discrimination. Drift diffusion modelling revealed increased sensory signal strength and decreased response caution and nondecision times as mechanisms underlying this effect of contingent rewards on pain discrimination. In addition, reinforcement learning models indicated a temporal evolution of discriminative abilities reflected by a trial-by-trial increase of perceived signal strength only with contingent rewards but not with noncontingent rewards. Modelling of separate learning rates for positive and negative prediction errors indicated that this temporal evolution of discriminative abilities was driven by positive reward prediction errors. These results might indicate increased sensitivity towards better-than-expected outcomes in the temporal adaptation of pain discrimination abilities to a rewarding context in humans.

Zero-echo time imaging achieves whole brain activity mapping without ventral signal loss in mice.

Functional MRI (fMRI) is an important tool for investigating functional networks. However, the widely used fMRI with T2*-weighted imaging in rodents has the problem of signal lack in the lateral ventral area of forebrain including the amygdala, which is essential for not only emotion but also noxious pain. Here, we scouted the zero-echo time (ZTE) sequence, which is robust to magnetic susceptibility and motion-derived artifacts, to image activation in the whole brain including the amygdala following the noxious stimulation to the hind paw. ZTE exhibited higher spatial and temporal signal-to-noise ratios than conventional fMRI sequences. Electrical sensory stimulation of the hind paw evoked ZTE signal increase in the primary somatosensory cortex. Formalin injection into the hind paw evoked early and latent change of ZTE signals throughout the whole brain including the subregions of amygdala. Furthermore, resting-state fMRI using ZTE demonstrated the functional connectivity, including that of the amygdala. These results indicate the feasibility of ZTE for whole brain fMRI including the amygdala and we first show acute and latent activity in different subnuclei of the amygdala complex after nociceptive stimulation.

Sensory experience controls dendritic structure and behavior by distinct pathways involving degenerins.

Dendrites are crucial for receiving information into neurons. Sensory experience affects the structure of these tree-like neurites, which, it is assumed, modifies neuronal function, yet the evidence is scarce, and the mechanisms are unknown. To study whether sensory experience affects dendritic morphology, we use the Caenorhabditis elegans' arborized nociceptor PVD neurons, under natural mechanical stimulation induced by physical contacts between individuals. We found that mechanosensory signals induced by conspecifics and by glass beads affect the dendritic structure of the PVD. Moreover, developmentally isolated animals show a decrease in their ability to respond to harsh touch. The structural and behavioral plasticity following sensory deprivation are functionally independent of each other and are mediated by an array of evolutionarily conserved mechanosensory amiloride-sensitive epithelial sodium channels (degenerins). Calcium imaging of the PVD neurons in a micromechanical device revealed that controlled mechanical stimulation of the body wall produces similar calcium dynamics in both isolated and crowded animals. Our genetic results, supported by optogenetic, behavioral, and pharmacological evidence, suggest an activity-dependent homeostatic mechanism for dendritic structural plasticity, that in parallel controls escape response to noxious mechanosensory stimuli.

Neurogenic inflammation and itch in barrier tissues.

Once regarded as distinct systems, the nervous system and the immune system are now recognized for their complex interactions within the barrier tissues. The neuroimmune circuitry comprises a dual-network system that detects external and internal disturbances, providing critical information to tailor a context-specific response to various threats to tissue integrity, such as wounding or exposure to noxious and harmful stimuli like pathogens, toxins, or allergens. Using the skin as an example of a barrier tissue with the polarized sensory neuronal responses of itch and pain, we explore the molecular pathways driving neuronal activation and the effects of this activation on the immune response. We then apply these findings to other barrier tissues, to find common pathways controlling neuroimmune responses in the barriers.

Local Administration of (-)-Epigallocatechin-3-Gallate as a Local Anesthetic Agent Inhibits the Excitability of Rat Nociceptive Primary Sensory Neurons.

While the impact of (-)-epigallocatechin-3-gallate (EGCG) on modulating nociceptive secondary neuron activity has been documented, it is still unknown how EGCG affects the excitability of nociceptive primary neurons in vivo. The objective of the current study was to investigate whether administering EGCG locally in rats reduces the excitability of nociceptive primary trigeminal ganglion (TG) neurons in response to mechanical stimulation in vivo. In anesthetized rats, TG neuronal extracellular single unit recordings were made in response to both non-noxious and noxious mechanical stimuli. Following the administration of EGCG, the mean firing rate of TG neurons to both non-noxious and noxious mechanical stimuli significantly decreased in a dose-dependent manner (1-10 mM), and both the non-noxious and nociceptive mechanical stimuli experienced the maximum suppression of discharge frequency within 5 min. These inhibitory effects lasted for approximately 20 min. These findings suggest that the local injection of EGCG into the peripheral receptive field suppresses the responsiveness of nociceptive primary sensory neurons in the TG, almost equal to that of the local anesthetic, 1% lidocaine. As a result, the local application of EGCG as a local anesthetic could alleviate nociceptive trigeminal pain that does not result in side effects, thereby playing a significant role in pain management.

Diffuse Noxious Inhibitory Controls in Chronic Pain States: Insights from Pre-Clinical Studies.

Diffuse noxious inhibitory control (DNIC), also known as conditioned pain modulation (CPM) in humans, is a paradigm wherein the heterotopic application of a noxious stimulus results in the attenuation of another spatially distant noxious input. The pre-clinical and clinical studies show the involvement of several neurochemical systems in DNIC/CPM and point to a major contribution of the noradrenergic, serotonergic, and opioidergic systems. Here, we thoroughly review the latest data on the monoaminergic and opioidergic studies, focusing particularly on pre-clinical models of chronic pain. We also conduct an in-depth analysis of these systems by integrating the available data with the descending pain modulatory circuits and the neurochemical systems therein to bring light to the mechanisms involved in the regulation of DNIC. The most recent data suggest that DNIC may have a dual outcome encompassing not only analgesic effects but also hyperalgesic effects. This duality might be explained by the underlying circuitry and the receptor subtypes involved therein. Acknowledging this duality might contribute to validating the prognostic nature of the paradigm. Additionally, DNIC/CPM may serve as a robust paradigm with predictive value for guiding pain treatment through more effective targeting of descending pain modulation.

A novel electroencephalographic evaluation of noxious stimulation during isoflurane anesthesia in dogs

In veterinary clinical medicine, evaluating the balance between nociception and antinociception presents a great challenge for anesthesiologists during canine surgeries. Heart rate (HR) and mean arterial pressure (MAP) are suitable indexes for monitoring noxious stimuli during anesthesia. Frontal electroencephalography (EEG) records, including processed parameters, are recommended for evaluating nociceptive balance in anesthetized unconscious human patients, which is unexplored in veterinary medicine. Therefore, the objective is to explore the response of processed EEG parameters to noxious stimulation and elucidate the impact of noxious stimulation on frontal cortical activity in dogs anesthetized with 1.5% isoflurane. Fourteen dogs were included and underwent frontal EEG monitoring, measuring the patient state index (PSI) and spectral edge frequency (SEF) before and after administering noxious stimulation using the towel clamp method on the tail of each 1.5% isoflurane-anesthetized dog. As the noxious stimulation was applied, there was a simultaneous increase in PSI, HR, and MAP, with PSI exhibiting a drastic response. SEF, especially on the left side, also increased with noxious stimulation. In EEG power spectral analysis, the delta band was decreased, and the alpha and beta bands showed an increase following noxious stimulation, with a more profound elevation of beta band on the left side. This study suggests that noxious stimulation brings asymmetric frontal cortical arousal, changing brain activity by suppressing delta wave and augmenting alpha and beta waves. Consequently, PSI seems to be a potential indicator for detecting stimuli in canine isoflurane anesthesia.

The Effects of Noxious Electrical Stimulation and Eccentric Exercise on Mechanical and Thermal Pain Sensitivity in Recreational Runners with Achilles Tendinopathy.

Achilles tendinopathy is a common overuse condition that can become persistent despite conservative treatment. Sensitization of both the peripheral and central nervous systems may contribute to the persistent pain. Both exercise and electrical stimulation have the potential to modulate the nervous system's sensitivity to painful stimuli. The purpose of this study was to describe the changes in pain sensitivity and self-reported function in runners with chronic Achilles tendon pain following sequential treatment with noxious electrical stimulation (NxES) and eccentric plantarflexion exercise. Single group, repeated measures design. Sixteen participants with chronic Achilles tendinopathy completed the Lower Extremity Functional Scale (LEFS) and the Victorian Institute of Sport Assessment-Achilles scale (VISA-A) and quantitative sensory tests (pressure pain threshold, heat temporal summation, and heat pain threshold) at baseline, one week, seven weeks, and then at a one month post intervention follow-up. The NxES was applied for one week, then followed by plantarflexion eccentric exercise for six weeks. Changes across timepoints were assessed using repeated measures ANOVA and post hoc analysis to describe differences. Hedges g effect sizes were also calculated. There was a significant improvement in LEFS (p < 0.001) and VISA-A (p < 0.001) from baseline to one month follow-up, with a mean change of 9.6 ± 7.7 and 19.4 ± 17.7 points respectively. Pressure pain threshold of the involved Achilles tendon increased over time (p < 0.001) with significant improvements after NxES application (p = 0.002) and after six weeks of eccentric exercise (p < 0.001). There were significant improvements from baseline to one month follow-up for heat temporal summation (p = 0.001) and heat pain threshold ( p < 0.001). For individuals with chronic Achilles tendinopathy, a sequential treatment of NxES followed by eccentric exercise resulted in a clinically significant improvement in self-reported pain and function. During the first week of treatment there was a reduction in mechanical hyperalgesia during the NxES-only phase, while a large reduction in primary heat hyperalgesia and additional desensitization to mechanical pain occurred during the eccentric training phase of treatment. 2b.

A nociceptor-specific RNAi screen in Drosophila larvae identifies RNA-binding proteins that regulate thermal nociception.

Nociception is the process by which sensory neurons detect and encode potentially harmful environmental stimuli to generate behavioral responses. Nociceptor neurons exhibit plasticity in which their sensitivity to noxious stimuli and subsequent ability to drive behavior may be altered by environmental conditions, injury, infection, and inflammation. In some cases, nociceptor sensitization requires regulated changes in gene expression, and recent studies have indicated roles for post-transcriptional mechanisms in regulating these changes as an aspect of nociceptor plasticity. The larvae of Drosophila melanogaster have been developed as a powerful model for studying mechanisms of nociception, nociceptor plasticity, and nociceptor development. Diverse RNA-binding proteins regulate the development and morphology of larval nociceptors, implying important roles for post-transcriptional regulation of gene expression in these neurons, but the importance of these mechanisms for nociceptive behavior has not been investigated systematically. In this study, we conducted a nociceptor-specific RNAi screen of 112 candidate RNA-binding protein genes to identify those that are required for normal sensitivity to noxious thermal stimuli. The screen and subsequent validation experiments identified nine candidate genes (eIF2α, eIF4A, eIF4AIII, eIF4G2, mbl, SC35, snf, Larp4B and CG10445) that produce defects in nociceptive response latency when knocked down in larval nociceptors. Some of the genes identified have well-understood roles in the regulation of translation initiation and regulation of nociceptor sensitization in vertebrate and invertebrate animal models, suggesting an evolutionarily conserved role for these mechanisms in regulating nociceptor sensitivity. Other screen isolates have previously described roles in regulating nociceptor morphology and mRNA processing, but less clear roles in regulating nociceptor function. Further studies will be necessary to identify the mechanisms by which the identified RNA-binding proteins regulate sensory neuron function and the identities of the mRNAs that they target.