UNASSIGNED: Advanced prosthetic hands may embed nanosensors and microelectronics in their cosmetic skin. Heat influx may cause damage to these delicate structures. Protecting the integrity of the prosthetic hand becomes critical and necessary to ensure sustainable function. This study aims to mimic the sensorimotor control strategy of the human hand in perceiving nociceptive stimuli and triggering self-protective mechanisms and to investigate how similar neuromorphic mechanisms implemented in prosthetic hand can allow amputees to both volitionally release a hot object upon a nociceptive warning and achieve reinforced release via a bionic withdrawal reflex.
UNASSIGNED: A steady-state temperature prediction algorithm was proposed to shorten the long response time of a thermosensitive temperature sensor. A hybrid sensory strategy for transmitting force and a nociceptive temperature warning using transcutaneous electrical nerve stimulation based on evoked tactile sensations was designed to reconstruct the nociceptive sensory loop for amputees. A bionic withdrawal reflex using neuromorphic muscle control technology was used so that the prosthetic hand reflexively opened when a harmful temperature was detected. Four able-bodied subjects and two forearm amputees randomly grasped a tube at the different temperatures based on these strategies.
UNASSIGNED: The average prediction error of temperature prediction algorithm was 8.30 ± 6.00%. The average success rate of six subjects in perceiving force and nociceptive temperature warnings was 86.90 and 94.30%, respectively. Under the reinforcement control mode in Test 2, the median reaction time of all subjects was 1.39 s, which was significantly faster than the median reaction time of 1.93 s in Test 1, in which two able-bodied subjects and two amputees participated. Results demonstrated the effectiveness of the integration of nociceptive sensory strategy and withdrawal reflex control strategy in a closed loop and also showed that amputees restored the warning of nociceptive sensation while also being able to withdraw from thermal danger through both voluntary and reflexive protection.
UNASSIGNED: This study demonstrated that it is feasible to restore the sensorimotor ability of amputees to warn and react against thermal nociceptive stimuli. Results further showed that the voluntary release and withdrawal reflex can work together to reinforce heat protection. Nevertheless, fusing voluntary and reflex functions for prosthetic performance in activities of daily living awaits a more cogent strategy in sensorimotor control.

Wind-up like pain or temporal summation of pain is a phenomenon in which pain sensation is increased in a frequency-dependent manner by applying repeated noxious stimuli of uniform intensity. Temporal summation in humans has been studied by observing the increase in pain or flexion reflex by repetitive electrical or thermal stimulations. Nonetheless, because the measurement is accompanied by severe pain, a minimally invasive method is desirable. Gradual augmentation of flexion reflex and pain induced by repetitive stimulation of the sural nerve was observed using three stimulation methods-namely, bipolar electrical, magnetic, and monopolar electrical stimulation, with 11 healthy male subjects in each group. The effects of frequency, intensity, and number of repetitive stimuli on the increase in the magnitude of flexion reflex and pain rating were compared among the three methods. The reflex was measured using electromyography (EMG) from the short head of the biceps femoris. All three methods produced a frequency- and intensity-dependent progressive increase in reflex and pain; pain scores were significantly lower for magnetic and monopolar stimulations than for bipolar stimulation (P < 0.05). The slope of increase in the reflex was steep during the first 4-6 stimuli but became gentler thereafter. In the initial phase, an increase in the reflex during the time before signals of C-fibers arrived at the spinal cord was observed in experiments using high-frequency stimulation, suggesting that wind-up was caused by inputs of A-fibers without the involvement of C-fibers. Magnetic and monopolar stimulations are minimally invasive and useful methods for observing the wind-up of the flexion reflex in humans. Monopolar stimulation is convenient because it does not require special equipment. There is at least a partial mechanism underlying the wind-up of the flexion reflex that does not require C-fibers.

Many neuroactive steroids induce sedation/hypnosis by potentiating γ-aminobutyric acid (GABAA) currents. However, we previously demonstrated that an endogenous neuroactive steroid epipregnanolone [(3β,5β)-3-hydroxypregnan-20-one] (EpiP) exerts potent peripheral analgesia and blocks T-type calcium currents while sparing GABAA currents in rat sensory neurons. This study seeks to investigate the behavioral effects elicited by systemic administration of EpiP and to characterize its use as an adjuvant agent to commonly used general anesthetics (GAs).
Here, we utilized electroencephalographic (EEG) recordings to characterize thalamocortical oscillations, as well as behavioral assessment and mouse genetics with wild-type (WT) and different knockout (KO) models of T-channel isoforms to investigate potential sedative/hypnotic and immobilizing properties of EpiP.
Consistent with increased oscillations in slower EEG frequencies, EpiP induced an hypnotic state in WT mice when injected alone intra-peritoneally (i.p.) and effectively facilitated anesthetic effects of isoflurane (ISO) and sevoflurane (SEVO). The CaV3.1 (Cacna1g) KO mice demonstrated decreased sensitivity to EpiP-induced hypnosis when compared to WT mice, whereas no significant difference was noted between CaV3.2 (Cacna1h), CaV3.3 (Cacna1i) and WT mice. Finally, when compared to WT mice, onset of EpiP-induced hypnosis was delayed in CaV3.2 KO mice but not in CaV3.1 and CaV3.3 KO mice.
We posit that EpiP may have an important role as novel hypnotic and/or adjuvant to volatile anesthetic agents. We speculate that distinct hypnotic effects of EpiP across all three T-channel isoforms is due to their differential expression in thalamocortical circuitry.

Introduction: Pain, temperament, fear, and anxiety can prevent safe and accurate evaluation of common neurologic reflexes in dogs. When sedation is used it is unknown how the neurological examination, and specifically patellar and withdrawal reflexes are affected, and, if present, how long any effect might last. The purpose of this study is to investigate the effect of sedation on the evaluation of select common limb spinal reflexes in healthy dogs. Material and Methods: Fourteen healthy dogs with normal neurologic exams were included. After placing joint landmarks, patellar reflex and pelvic and thoracic limb withdrawal reflexes were tested. Joint angles were measured, obtaining reflex angle endpoints, change in angle, and change in time to reflex completion. These measurements were recorded at different time points: prior to sedation (awake timepoint), 15 and 30 min following administration of standardized sedation protocol of dexmedetomidine and butorphanol, and 15 and 30 min following administration of a standardized reversal agent, atipamazole. Results: For patellar reflex, the stifle end angle increased from 91.5 to 108.55 degrees (p < 0.0001) 15 min following sedation, and remained increased at 104.5 degrees (p < 0.0001) 30 min following sedation. Stifle change in angle increased from 9.6 to 24.4 degrees (p < 0.0001) 15 min following sedation, and remained increased at 20.85 degrees (p < 0.0001) and 11 degrees (p = 0.012) at 30 min sedation and 15 min reversal. Tarsal joint in pelvic withdrawal and elbow in thoracic withdrawal reflexes did not differ in at any timepoint of sedation or reversal when compared with the awake timepoint, for end angle or change in angle. The increases in end angle and change in angle for patellar reflex generated a change in time for patellar reflex from 0.12 s (awake) to 0.129 s (15 min sedation) which was statistically significant (p = 0.041). Change in time did not differ for pelvic withdrawal or thoracic withdrawal. Discussion/Conclusions: Reflexes were elicited in all dogs under sedation. Sedation does not affect the evaluation of the withdrawal reflex on any limb but improves the visualization of the patellar reflex in this group of neurologically normal dogs.

The primary somatosensory cortex (S1) comprises a number of functionally distinct regions, reflecting the diversity of somatosensory receptor submodalities innervating the body. In particular, two spatially and functionally distinct nociceptive regions have been described in primate S1 (Vierck et al., 2013; Whitsel et al., 2019). One region is located mostly in Brodmann cytoarchitectonic area 1, where a subset of neurons exhibit functional characteristics associated with myelinated Aδ nociceptors and perception of 1st/sharp, discriminative pain. The second region is located at the transition between S1 and primary motor cortex (M1) in area 3a, where neurons exhibit functional characteristics associated with unmyelinated C nociceptors and perception of 2nd/slow, burning pain. To test the hypothesis that in rats the transitional zone (TZ) - which is a dysgranular region at the transition between M1 and S1 - is the functional equivalent of the nociresponsive region of area 3a in primates, extracellular spike discharge activity was recorded from TZ neurons in rats under general isoflurane anesthesia. Thermonoxious stimuli were applied by lowering the contralateral forepaw or hindpaw into a 48-51 °C heated water bath for 5-10 s. Neurons in TZ were found to be minimally affected by non-noxious somatosensory stimuli, but highly responsive to thermonoxious skin stimuli in a slow temporal summation manner closely resembling that of nociresponsive neurons in primate area 3a. Selective inactivation of TZ by topical lidocaine application suppressed or delayed the nociceptive withdrawal reflex, suggesting that TZ exerts a tonic facilitatory influence over spinal cord neurons producing this reflex. In conclusion, TZ appears to be a rat homolog of the nociresponsive part of monkey area 3a. A possibility is considered that this region might be primarily engaged in autonomic aspects of nociception.

OBJECTIVE: To describe the prevalence, signalment, clinical features, etiology, and outcome in dogs with acute thoracolumbar disease and suspected spinal shock.
METHODS: Retrospective clinical case study (2005-2010).
METHODS: Private specialty practice.
METHODS: Medical records of 263 dogs with thoracolumbar spinal magnetic resonance imaging were reviewed. If decreased or absent withdrawal reflexes were present in 1 or both pelvic limbs, in the absence of a spinal lesion in the lumbosacral intumescence, dogs were diagnosed with spinal shock. Dogs with suspected or confirmed spinal neoplasia, myelomalacia, or meningomyelitis were excluded. Seventeen of 263 dogs (6%) met inclusion criteria.
METHODS: None.
RESULTS: Thoracic lesions were significantly more likely to result in spinal shock when compared to lumbar lesions (P = 0.03). Fibrocartilaginous embolism was the most commonly diagnosed etiology (7 of 17 dogs), and was more common in the thoracic spine compared to in the lumbar spine (P = 0.10). Six of 17 dogs (35%) were diagnosed with intervertebral disk herniation; 4 of 17 dogs (24%) with suspected acute noncompressive nucleus pulposus extrusion. Two dogs were lost to follow-up. Fourteen of 15 (93%) dogs had improved or normal reflexes by 60 days post injury.
CONCLUSIONS: Although the prevalence of spinal shock was low, it should be considered in any dog presenting with an acute history of thoracolumbar spinal injury with reduced or absent reflexes in the pelvic limbs. The presence of spinal shock should not dissuade a veterinarian from pursuing appropriate diagnostic testing and therapy for the underlying etiology.

OBJECTIVE: To explore whether the trigeminocervical reflexes (TCRs) show a reflex receptive field organization in the brainstem.
METHODS: The facial skin of 16 healthy subjects was electrically stimulated at nine sites reflecting the distribution of the three branches of the trigeminal nerve. The reflex-evoked EMG responses were measured bilaterally from the neck muscles and the head and neck kinematic reactions were detected.
RESULTS: TCRs are site dependent. There was a vertical gradient in the magnitude of the reflex responses. EMG and kinematic reflexes were larger when evoked from ophthalmic and maxillary sites than from mandibular ones. The reflex responses exhibited a crossed right-left behavior. Stimulation of the lateral sites evoked larger reflex responses in the contralateral trapezium muscle as well as head rotation and neck bending away from the stimulated side.
CONCLUSIONS: This modular arrangement of the TCRs seems to be related to withdrawal strategies aimed at protecting the face from injuries, in accordance with the functional role that each group of muscles plays in head and neck motion.
CONCLUSIONS: It is likely that the CNS may exploit the neck muscle synergies revealed by the painful stimulation of the skin face in order to control the head and neck movements.

The aim of this study was to evaluate the effectiveness of three local, topical anesthetics on touch response thresholds of the paws of 1-day-old rats. Touch response thresholds were measured using Semmes Weinstein monofilaments after treatment of the paws with EMLA (2.5% lidocaine and 2.5% prilocaine), alcaine (.5% proparacaine), triocaine (20% benzocaine, 6% lidocaine, and 4% tetracaine), or petroleum jelly (treatment control). Touch thresholds significantly increased after treatment with EMLA 18% of the time, and there was no evidence of a systemic effect. Touch thresholds were not significantly altered after treatment with alcaine, triocaine, or petroleum jelly. Therefore, EMLA appears to be a slightly effective topical anesthetic for reducing tactile sensitivity in newborn rats.