Gate control of sensory neurotransmission in peripheral ganglia by proprioceptive sensory neurons.

Melzak and Wall's gate control theory proposed that innocuous input into the dorsal horn of the spinal cord represses pain-inducing nociceptive input. Here we show that input from proprioceptive parvalbumin-expressing sensory neurons tonically represses nociceptor activation within dorsal root ganglia. Deletion of parvalbumin-positive sensory neurons leads to enhanced nociceptor activity measured with GCaMP3, increased input into wide dynamic range neurons of the spinal cord and increased acute and spontaneous pain behaviour, as well as potentiated innocuous sensation. Parvalbumin-positive sensory neurons express the enzymes and transporters necessary to produce vesicular GABA that is known to be released from depolarized somata. These observations support the view that gate control mechanisms occur peripherally within dorsal root ganglia.

The efficacy of various interventions as good strategies to reduce pain in botulinum neurotoxin A for wrinkles. A systematic review of the randomized controlled trials (RCTs).

Various topical interventions have been described to minimize botulinum neurotoxin-A (BoNT)-induced pain. The purpose of this study is to conduct a systematic review of relevant randomized controlled trials (RCTs) to compare the efficacy of pain relief methods during BoNT injection. PubMed, Scopus, and Web of Science were searched using "Botox," "Botulinum," or "BTX." We identified RCTs in which BoNT were injected to eliminate wrinkles. The pain score was the study outcome, and pain reduction method was compared with routine one. The meta-analysis was reported using the PRISMA checklist. The Higgins I(I2) statistical model assessed results heterogeneity. Two thousand one hundred and twenty-three articles were identified, thirteen articles eligible. Two hundred and sixty-two healthy volunteers were performed on these RCTs. Meta-analysis evaluated different methods to ease BoNT injection pain, and these methods significantly improved outcomes by 0.23% (95%CI, 0.11-0.46, p = .000). Subgroup analysis based on injection area showed no significant heterogeneity, but heterogeneity decreased when subgroup analysis based on other methods was done (Cochran's Q test = 115.52, p = .0001, I2 = 87.9%). This meta-analysis confirms the effectiveness of pain relief methods during BoNT injection. Evaluation of different methods showed their effectiveness, but finding the best method requires comparative studies, although the role of pH and EMLA has been proven.

Research on Gate Opening Control Based on Improved Beetle Antennae Search.

To address the issues of sluggish response and inadequate precision in traditional gate opening control systems, this study presents a novel approach for direct current (DC) motor control utilizing an enhanced beetle antennae search (BAS) algorithm to fine-tune the parameters of a fuzzy proportional integral derivative (PID) controller. Initially, the mathematical model of the DC motor drive system is formulated. Subsequently, employing a search algorithm, the three parameters of the PID controller are optimized in accordance with the control requirements. Next, software simulation is employed to analyze the system's response time and overshoot. Furthermore, a comparative analysis is conducted between fuzzy PID control based on the improved beetle antennae search algorithm, and conventional approaches such as the traditional beetle antennae search algorithm, the traditional particle swarm algorithm, and the enhanced particle swarm algorithm. The findings indicate the superior performance of the proposed method, characterized by reduced oscillations and accelerated convergence compared to the alternative methods.

Excitatory and Inhibitory Neurons of the Spinal Cord Superficial Dorsal Horn Diverge in Their Somatosensory Responses and Plasticity in Vivo.

The superficial dorsal horn (SDH) of the spinal cord represents the first site of integration between innocuous and noxious somatosensory stimuli. According to gate control theory, diverse populations of excitatory and inhibitory interneurons within the SDH are activated by distinct sensory afferents, and their interplay determines the net nociceptive output projecting to higher pain centers. Although specific SDH cell types are ill defined, numerous classifications schemes find that excitatory and inhibitory neurons fundamentally differ in their morphology, electrophysiology, neuropeptides, and pain-associated plasticity; yet little is known about how these neurons respond over a range of natural innocuous and noxious stimuli. To address this question, we applied an in vivo imaging approach in male mice where the genetically encoded calcium indicator GCaMP6s was expressed either in vGluT2-positive excitatory or vIAAT-positive inhibitory neurons. We found that inhibitory neurons were markedly more sensitive to innocuous touch than excitatory neurons but still responded dynamically over a wide range of noxious mechanical stimuli. Inhibitory neurons were also less sensitive to thermal stimuli than their excitatory counterparts. In a capsaicin model of acute pain sensitization, the responses of excitatory neurons were significantly potentiated to innocuous and noxious mechanical stimuli, whereas inhibitory neural responses were only depressed to noxious stimuli. These in vivo findings show that excitatory and inhibitory SDH neurons diverge considerably in their somatosensory responses and plasticity, as postulated by gate control theory.SIGNIFICANCE STATEMENT Gate control theory posits that opposing spinal excitatory and inhibitory neurons, differently tuned across somatosensory modalities, determine the net nociceptive output to higher pain centers. Little is known about how natural stimuli activate these two neural populations. This study applied an in vivo calcium imaging approach to genetically target these neurons and contrast their responses over a range of innocuous and noxious mechanical and thermal stimuli. Compared with excitatory neurons, we found that inhibitory neurons are more sensitive to innocuous touch and far less sensitive to thermal stimuli. An acute model of pain also revealed that these subtypes undergo divergent mechanosensory plasticity. Our data provide important and novel insights for gate-control inspired models of pain processing.

Massaging as a pain-relieving intervention before performing intravenous access.

PURPOSE: Pain is "an unpleasant sensory and emotional experience arising from actual or potential tissue damage or described in terms of damage". Stimulating the skin by rubbing, stroking, massaging, or applying pressure near the injection site is pain-relieving. Needle-related procedures induce anxiety, distress, and fear in children and adults. The present study aimed to test the effectiveness of massaging the access site in reducing pain associated with intravenous access. DESIGN: After obtaining institutional ethics committee approval, this prospective randomized single-blinded study was performed on 250 ASA I-II patients 18 to 65 years old, scheduled for elective minor general surgery under general anaesthesia. METHODS: Patients were randomized into the Massaging Group (MG) and the Control Group (CG). A Situational Trait Anxiety Inventory (STAI) was conducted to evaluate the anxiety levels of the patients. In addition, the skin adjacent to the intravenous access site was massaged for 15 s in circular motions with moderate intensity by the investigator's right thumb before performing the intravenous access in the MG. The CG did not receive any massage adjacent to the access site. The primary endpoint, the intensity of perceived pain, was rated on a non-graduated 10-cm Visual Analogue Score (VAS). FINDINGS: The groups' demographic data and STAI I-II scores were similar. There was a significant difference between the VAS scores of the two groups (p < 0.05). CONCLUSIONS: Our results support massaging as an effective pain-relieving technique before intravenous intervention. As massaging is a universal and non-invasive intervention that requires no advanced preparation, we recommend massaging before each intravenous cannulation to reduce pain caused by intravenous access.

Primary Afferent Depolarization and the Gate Control Theory of Pain: A Tutorial Simulation.

The gate control theory of pain postulates that the sensation of pain can be reduced or blocked by closing a "gate" at the earliest synaptic level in the spinal cord, where nociceptive (pain) afferents excite the ascending interneurons that transmit the signal to the brain. Furthermore, the gate can be induced to close by stimulating touch afferents with receptive fields in the same general area as the trauma that is generating the pain (the "rub it to make it better" effect). A considerable volume of research has substantiated the theory and shown that a key mechanism mediating the gate is pre-synaptic inhibition, and that this inhibition is generated by depolarizing IPSPs in the nociceptor central terminals (primary afferent depolarization; PAD). Both pre-synaptic inhibition and depolarizing IPSPs are topics that students often regard as matters of secondary importance (if they are aware of them at all), and yet they are crucial to a matter of primary importance to us all - pain control. This report describes some simple computer simulations that illustrate pre-synaptic inhibition and explore the importance of the depolarizing aspect of the IPSPs. These concepts are then built into a model of the gate control of pain itself. Finally, the simulations show how a small change in chloride homeostasis can generate the dorsal root reflex, in which nociceptor afferents generate antidromic spikes which may increase neurogenic inflammation and actually exacerbate pain. The hope is that the simulations will increase awareness and understanding of a topic that is important in both basic neuroscience and medical neurology.

Dorsal column and root stimulation at Aß-fiber intensity activate superficial dorsal horn glutamatergic and GABAergic populations.

Neurostimulation therapies are frequently used in patients with chronic pain conditions. They emerged from Gate Control Theory (GCT), which posits that Aß-fiber activation recruits superficial dorsal horn (SDH) inhibitory networks to "close the gate" on nociceptive transmission, resulting in pain relief. However, the efficacy of current therapies is limited, and the underlying circuits remain poorly understood. For example, it remains unknown whether ongoing stimulation of Aß-fibers is sufficient to drive activity in SDH neurons. We used multiphoton microscopy in spinal cords extracted from mice expressing the genetically encoded calcium indicator GCaMP6s in glutamatergic and GABAergic populations; activity levels were inferred from deconvolved calcium signals using CaImAn software. Sustained Aß-fiber stimulation at the dorsal columns or dorsal roots drove robust yet transient activation of both SDH populations. Following the initial increase, activity levels decreased below baseline in glutamatergic neurons and were depressed after stimulation ceased in both populations. Surprisingly, only about half of GABAergic neurons responded to Aß-fiber stimulation. This subset showed elevated activity for the entire duration of stimulation, while non-responders decreased with time. Our findings suggest that Aß-fiber stimulation initially recruits both excitatory and inhibitory populations but has divergent effects on their activity, providing a foundation for understanding the analgesic effects of neurostimulation devices.Perspective: This article used microscopy to characterize the responses of mouse spinal cord cells to stimulation of non-painful nerve fibers. These findings deepen our understanding of how the spinal cord processes information and provide a foundation for improving pain-relieving therapies.

Spinal Circuits for Touch, Pain, and Itch.

The exteroceptive somatosensory system is important for reflexive and adaptive behaviors and for the dynamic control of movement in response to external stimuli. This review outlines recent efforts using genetic approaches in the mouse to map the spinal cord circuits that transmit and gate the cutaneous somatosensory modalities of touch, pain, and itch. Recent studies have revealed an underlying modular architecture in which nociceptive, pruritic, and innocuous stimuli are processed by distinct molecularly defined interneuron cell types. These include excitatory populations that transmit information about both innocuous and painful touch and inhibitory populations that serve as a gate to prevent innocuous stimuli from activating the nociceptive and pruritic transmission pathways. By dissecting the cellular composition of dorsal-horn networks, studies are beginning to elucidate the intricate computational logic of somatosensory transformation in health and disease.

LGCCT: A Light Gated and Crossed Complementation Transformer for Multimodal Speech Emotion Recognition.

Semantic-rich speech emotion recognition has a high degree of popularity in a range of areas. Speech emotion recognition aims to recognize human emotional states from utterances containing both acoustic and linguistic information. Since both textual and audio patterns play essential roles in speech emotion recognition (SER) tasks, various works have proposed novel modality fusing methods to exploit text and audio signals effectively. However, most of the high performance of existing models is dependent on a great number of learnable parameters, and they can only work well on data with fixed length. Therefore, minimizing computational overhead and improving generalization to unseen data with various lengths while maintaining a certain level of recognition accuracy is an urgent application problem. In this paper, we propose LGCCT, a light gated and crossed complementation transformer for multimodal speech emotion recognition. First, our model is capable of fusing modality information efficiently. Specifically, the acoustic features are extracted by CNN-BiLSTM while the textual features are extracted by BiLSTM. The modality-fused representation is then generated by the cross-attention module. We apply the gate-control mechanism to achieve the balanced integration of the original modality representation and the modality-fused representation. Second, the degree of attention focus can be considered, as the uncertainty and the entropy of the same token should converge to the same value independent of the length. To improve the generalization of the model to various testing-sequence lengths, we adopt the length-scaled dot product to calculate the attention score, which can be interpreted from a theoretical view of entropy. The operation of the length-scaled dot product is cheap but effective. Experiments are conducted on the benchmark dataset CMU-MOSEI. Compared to the baseline models, our model achieves an 81.0% F1 score with only 0.432 M parameters, showing an improvement in the balance between performance and the number of parameters. Moreover, the ablation study signifies the effectiveness of our model and its scalability to various input-sequence lengths, wherein the relative improvement is almost 20% of the baseline without a length-scaled dot product.

Presenting a Neuroid model of wind-up based on dynamic synapse.

The treatment of chronic pain depends mainly on our understanding of the mechanisms such as central sensitization which is involved in it. Wind-up of spinal cord is one of the most important phenomena in the study of central sensitization which has received considerable attention in recent years. Wind-up is a form of short-term synaptic plasticity (STP) that can lead to central sensitivity. Although several models have been proposed for wind-up, none of them are based on the experimental evidence. In this study, a new network model is introduced according to the gate control theory of pain. Neuroids are used as neuron models in which their parameters are captured from available experimental data. Adjusting the weights of the network is based on the short-term synaptic plasticity. The results of the time and frequency domain show that the model can well simulate wind-up behavior. This model can be used for analyzing, predicting and controlling chronic pain in the future.

When does the brain choose pain?

Why does the brain choose pain? Why does an organ that is able to mask pain, even when intense as in fractures or in fighting wounds, decide to let pain pass and begin conscious, such as that of migraine, when there is no noxa patogena and there is no threat to the integrity of the organism, failing in the main function of pain, that of protection? In this brief review, we retrace the journey that led to the identification of the first complex mechanism of regulation of painful input, the spinal gate control system, through the identification of the predominantly thalamocortical supraspinal centers of the neuromatrix, up to the recognition of a pain matrix extremely articulate and sophisticated that integrates elementary sensations with much more complex functions, related to memory, affectivity, emotion, autonomic self-regulation, and homeostasis systems and so on. Why does the protection system lose its fundamental function in migraine in a behavioral harakiri that periodically damages only itself? This is the challenge facing those dealing with primary headaches in the next future: why migraine? The great strides made in the last decades that have led to the understanding of complex pathogenetic mechanisms risk remaining orphans if we fail to identify the primum movens at the base of one of the most common pathologies in the human race.

Buzzing away the pain: Using an electric toothbrush for vibration anesthesia during painful procedures.

Many dermatologic procedures are painful and traumatic, for both pediatric patients and providers alike. Vibration anesthesia has recently been discussed as an effective method for reducing pain associated with injections, but some vibration machines can be cost prohibitive for providers. We describe how to employ an electric toothbrush as an inexpensive and effective option to provide vibration anesthesia during painful pediatric procedures.

Low-threshold mechanoreceptors play a frequency-dependent dual role in subjective ratings of mechanical allodynia.

In the setting of injury, myelinated primary afferent fibers that normally signal light touch are thought to switch modality and instead signal pain. In the absence of injury, touch is perceived as more intense when firing rates of Aß afferents increase. However, it is not known if varying the firing rates of Aß afferents have any consequence to the perception of dynamic mechanical allodynia (DMA). We hypothesized that, in the setting of injury, the unpleasantness of DMA would be intensified as the firing rates of Aß afferents increase. Using a stimulus-response protocol established in normal skin, where an increase in brush velocity results in an increase of Aß afferent firing rates, we tested if brush velocity modulated the unpleasantness of capsaicin-induced DMA. We analyzed how changes in estimated low-threshold mechanoreceptor firing activity influenced perception and brain activity (functional MRI) of DMA. Brushing on normal skin was perceived as pleasant, but brushing on sensitized skin produced both painful and pleasant sensations. Surprisingly, there was an inverse relationship between Aß firing rates and unpleasantness such that brush stimuli that produced low firing rates were most painful and those that elicited high firing rates were rated as pleasant. Concurrently to this, we found increased cortical activity in response to low Aß firing rates in regions previously implicated in pain processing during brushing of sensitized skin, but not normal skin. We suggest that Aß signals do not merely switch modality to signal pain during injury. Instead, they exert a high- and low-frequency-dependent dual role in the injured state, with respectively both pleasant and unpleasant consequences. NEW & NOTEWORTHY We suggest that Aß signals do not simply switch modality to signal pain during injury but play a frequency-dependent and dual role in the injured state with both pleasant and unpleasant consequences. These results provide a framework to resolve the apparent paradox of how touch can inhibit pain, as proposed by the Gate Control Theory and the existence of dynamic mechanical allodynia.

Transcutaneous electrical nerve stimulation reduces exercise-induced perceived pain and improves endurance exercise performance.

PURPOSE: Muscle pain is a natural consequence of intense and prolonged exercise and has been suggested to be a limiter of performance. Transcutaneous electrical nerve stimulation (TENS) and interferential current (IFC) have been shown to reduce both chronic and acute pain in a variety of conditions. This study sought to ascertain whether TENS and IFC could reduce exercise-induced pain (EIP) and whether this would affect exercise performance. It was hypothesised that TENS and IFC would reduce EIP and result in an improved exercise performance. METHODS: In two parts, 18 (Part I) and 22 (Part II) healthy male and female participants completed an isometric contraction of the dominant bicep until exhaustion (Part I) and a 16.1 km cycling time trial as quickly as they could (Part II) whilst receiving TENS, IFC, and a SHAM placebo in a repeated measures, randomised cross-over, and placebo-controlled design. Perceived EIP was recorded in both tasks using a validated subjective scale. RESULTS: In Part I, TENS significantly reduced perceived EIP (mean reduction of 12%) during the isometric contraction (P = 0.006) and significantly improved participants' time to exhaustion by a mean of 38% (P = 0.02). In Part II, TENS significantly improved (P = 0.003) participants' time trial completion time (~2% improvement) through an increased mean power output. CONCLUSION: These findings demonstrate that TENS can attenuate perceived EIP in a healthy population and that doing so significantly improves endurance performance in both submaximal isometric single limb exercise and whole-body dynamic exercise.

Conventional and Novel Spinal Stimulation Algorithms: Hypothetical Mechanisms of Action and Comments on Outcomes.

OBJECTIVE: Spinal cord stimulation (SCS) emerged as a direct clinical spin-off from the Gate Control Theory from 1965. Over the last decade, several new modes of SCS have appeared. This review discusses these novel techniques and their hypothetical mechanisms of action. MATERIAL AND METHODS: A recent literature search on SCS coupled with the most recent data from poster presentations and congress lectures have been used to illustrate new hypothetical ways of modulating pain. RESULTS: Several physiological and neurochemical mechanisms for conventional paresthetic SCS have been described in detail. However, much less is known about the novel SCS modes of action. One new algorithm utilizes very high frequencies (up to 10 kHz) intended for direct stimulation of dorsal horns at the T9-T10 level to treat both low back pain and leg pain. Another technique uses bursts of impulses with a high internal frequency delivered to the dorsal spinal cord with a frequency of 40 Hz. Both of these therapies intend to be subparesthetic and effective both for neuropathic and nociceptive pain components. During the last few years, more moderate changes in SCS parameters have been tried in order to increase the amount of electric charge passed from the lead to the neural tissue. This strategy, called "high density SCS," utilizes frequencies up to 1200 Hz or long pulse widths. CONCLUSIONS: The present SCS therapies have developed beyond the Gate Control Concept. New hypotheses about mechanisms of action are presented and some improved results are discussed.

Spinal sensory projection neuron responses to spinal cord stimulation are mediated by circuits beyond gate control.

Spinal cord stimulation (SCS) is a therapy used to treat intractable pain with a putative mechanism of action based on the Gate Control Theory. We hypothesized that sensory projection neuron responses to SCS would follow a single stereotyped response curve as a function of SCS frequency, as predicted by the Gate Control circuit. We recorded the responses of antidromically identified sensory projection neurons in the lumbar spinal cord during 1- to 150-Hz SCS in both healthy rats and neuropathic rats following chronic constriction injury (CCI). The relationship between SCS frequency and projection neuron activity predicted by the Gate Control circuit accounted for a subset of neuronal responses to SCS but could not account for the full range of observed responses. Heterogeneous responses were classifiable into three additional groups and were reproduced using computational models of spinal microcircuits representing other interactions between nociceptive and nonnociceptive sensory inputs. Intrathecal administration of bicuculline, a GABAA receptor antagonist, increased spontaneous and evoked activity in projection neurons, enhanced excitatory responses to SCS, and reduced inhibitory responses to SCS, suggesting that GABAA neurotransmission plays a broad role in regulating projection neuron activity. These in vivo and computational results challenge the Gate Control Theory as the only mechanism underlying SCS and refine our understanding of the effects of SCS on spinal sensory neurons within the framework of contemporary understanding of dorsal horn circuitry.

Nonpharmacologic approaches for pain management during labor compared with usual care: a meta-analysis.

OBJECTIVES: To assess the effects of nonpharmacologic approaches to pain relief during labor, according to their endogenous mechanism of action, on obstetric interventions, maternal, and neonatal outcomes. DATA SOURCE: Cochrane library, Medline, Embase, CINAHL and the MRCT databases were used to screen studies from January 1990 to December 2012. STUDY SELECTION: According to Cochrane criteria, we selected randomized controlled trials that compared nonpharmacologic approaches for pain relief during labor to usual care, using intention-to-treat method. RESULTS: Nonpharmacologic approaches, based on Gate Control (water immersion, massage, ambulation, positions) and Diffuse Noxious Inhibitory Control (acupressure, acupuncture, electrical stimulation, water injections), are associated with a reduction in epidural analgesia and a higher maternal satisfaction with childbirth. When compared with nonpharmacologic approaches based on Central Nervous System Control (education, attention deviation, support), usual care is associated with increased odds of epidural OR 1.13 (95% CI 1.05-1.23), cesarean delivery OR 1.60 (95% CI 1.18-2.18), instrumental delivery OR 1.21 (95% CI 1.03-1.44), use of oxytocin OR 1.20 (95% CI 1.01-1.43), labor duration (29.7 min, 95% CI 4.5-54.8), and a lesser satisfaction with childbirth. Tailored nonpharmacologic approaches, based on continuous support, were the most effective for reducing obstetric interventions. CONCLUSION: Nonpharmacologic approaches to relieve pain during labor, when used as a part of hospital pain relief strategies, provide significant benefits to women and their infants without causing additional harm.

Mechanism of dorsal column stimulation to treat neuropathic but not nociceptive pain: analysis with a computational model.

OBJECTIVE: Stimulation of axons within the dorsal columns of the human spinal cord has become a widely used therapy to treat refractory neuropathic pain. The mechanisms have yet to be fully elucidated and may even be contrary to standard "gate control theory." Our hypothesis is that a computational model provides a plausible description of the mechanism by which dorsal column stimulation (DCS) inhibits wide dynamic range (WDR) cell output in a neuropathic model but not in a nociceptive pain model. MATERIALS AND METHODS: We created a computational model of the human spinal cord involving approximately 360,000 individual neurons and dendritic processing of some 60 million synapses--the most elaborate dynamic computational model of the human spinal cord to date. Neuropathic and nociceptive "pain" signals were created by activating topographically isolated regions of excitatory interneurons and high-threshold nociceptive fiber inputs, driving analogous regions of WDR neurons. Dorsal column fiber activity was then added at clinically relevant levels (e.g., Aß firing rate between 0 and 110 Hz by using a 210-µsec pulse width, 50-150 Hz frequency, at 1-3 V amplitude). RESULTS: Analysis of the nociceptive pain, neuropathic pain, and modulated circuits shows that, in contradiction to gate control theory, 1) nociceptive and neuropathic pain signaling must be distinct, and 2) DCS neuromodulation predominantly affects the neuropathic signal only, inhibiting centrally sensitized pathological neuron groups and ultimately the WDR pain transmission cells. CONCLUSION: We offer a different set of necessary premises than gate control theory to explain neuropathic pain inhibition and the relative lack of nociceptive pain inhibition by using retrograde DCS. Hypotheses regarding not only the pain relief mechanisms of DCS were made but also regarding the circuitry of pain itself, both nociceptive and neuropathic. These hypotheses and further use of the model may lead to novel stimulation paradigms.

Enhanced Multitask Learning for Hash Code Generation of Palmprint Biometrics.

This paper presents a novel multitask learning framework for palmprint biometrics, which optimizes classification and hashing branches jointly. The classification branch within our framework facilitates the concurrent execution of three distinct tasks: identity recognition and classification of soft biometrics, encompassing gender and chirality. On the other hand, the hashing branch enables the generation of palmprint hash codes, optimizing for minimal storage as templates and efficient matching. The hashing branch derives the complementary information from these tasks by amalgamating knowledge acquired from the classification branch. This approach leads to superior overall performance compared to individual tasks in isolation. To enhance the effectiveness of multitask learning, two additional modules, an attention mechanism module and a customized gate control module, are introduced. These modules are vital in allocating higher weights to crucial channels and facilitating task-specific expert knowledge integration. Furthermore, an automatic weight adjustment module is incorporated to optimize the learning process further. This module fine-tunes the weights assigned to different tasks, improving performance. Integrating the three modules above has shown promising accuracies across various classification tasks and has notably improved authentication accuracy. The extensive experimental results validate the efficacy of our proposed framework.

Bridging Old and New in Pain Medicine: An Historical Review.

Pain is both one of the oldest complaints known to medicine and a field for some of medicine's latest breakthroughs and innovations. Pharmacologic treatment of pain is one of the oldest remedies, and opioids have been used since ancient times as an effective pain reliever but with certain specific risks for abuse. Greater knowledge of opioids led to a more thorough understanding of the complexities of pain, which may have any number of mechanisms. A greater understanding of nerve fibers and pain signaling led to the development of more drugs and the more targeted delivery of analgesics using the hollow needle. The hollow needle changed pain treatment and led to percutaneous injections and what would later become interventional pain medicine with regional anesthesia and nerve blocks. Today, imaging can be combined with interventional techniques for more precise localization of nerves for diagnosis and treatment. The role of artificial intelligence in interventional pain medicine, especially in imaging for interventional procedures, remains unknown but will likely become extremely beneficial.