Pain is a complex multidimensional experience encompassing sensory-discriminative, affective-motivational and cognitive-emotional components mediated by different neural mechanisms. Investigations of neurophysiological signals from simultaneous recordings of two or more cortical circuits may reveal important circuit mechanisms on cortical pain processing. The anterior cingulate cortex (ACC) and primary somatosensory cortex (S1) represent two most important cortical circuits related to sensory and affective processing of pain. Here, we recorded in vivo extracellular activity of the ACC and S1 simultaneously from male adult Sprague-Dale rats ( n = 5), while repetitive noxious laser stimulations were delivered to animalÕs hindpaw during pain experiments. We identified spontaneous pain-like events based on stereotyped pain behaviors in rats. We further conducted systematic analyses of spike and local field potential (LFP) recordings from both ACC and S1 during evoked and spontaneous pain episodes. From LFP recordings, we found stronger phase-amplitude coupling (theta phase vs. gamma amplitude) in the S1 than the ACC ( n = 10 sessions), in both evoked ( p = 0.058) and spontaneous pain-like behaviors ( p = 0.017, paired signed rank test). In addition, pain-modulated ACC and S1 neuronal firing correlated with the amplitude of stimulus-induced event-related potentials (ERPs) during evoked pain episodes. We further designed statistical and machine learning methods to detect pain signals by integrating ACC and S1 ensemble spikes and LFPs. Together, these results reveal differential coding roles between the ACC and S1 in cortical pain processing, as well as point to distinct neural mechanisms between evoked and putative spontaneous pain at both LFP and cellular levels.
Chronic pain is characterized by discrete pain episodes of unpredictable frequency and duration. This hinders the study of pain mechanisms, and contributes to the use of pharmacological treatments associated with side effects, addiction and drug tolerance. Here, we show that a closed-loop brain–machine interface (BMI) can modulate sensory-affective experiences in real time in freely behaving rats by coupling neural codes for nociception directly with therapeutic cortical stimulation. The BMI decodes the onset of nociception via a state-space model on the basis of the analysis of online-sorted spikes recorded from the anterior cingulate cortex (which is critical for pain processing), and couples real-time pain detection with optogenetic activation of the prelimbic prefrontal cortex (which exerts top–down nociceptive regulation). In rats, the BMI effectively inhibited sensory and affective behaviors caused by acute mechanical or thermal pain, and by chronic inflammatory or neuropathic pain. The approach provides a blueprint for demand-based neuromodulation to treat sensory-affective disorders, and could be further leveraged for nociceptive control and to study pain mechanisms.
Background: This study aimed to examine the relationship between anatomical surface landmarks in fresh frozen cadavers as related to in vivo endoscopic trigger finger release (ETFR) and present clinical outcomes after a single-portal antegrade ETFR technique. Methods: Endoscopic trigger finger release was performed on 40 cadaveric digits. Each digit was dissected and the following measurements were recorded: distance from palmar digital crease and A1 pulley, length of the A1 pulley, percentage of A1 pulley released, and injury to vulnerable anatomy. A retrospective chart review was performed on 48 patients (62 digits) treated with ETFR. Outcome measures included grip and pinch strength, range of motion, Disability of Arm, Shoulder, and Hand (DASH) questionnaires, and Visual Analog Scale (VAS) pain scores. Results: Release of the A1 pulley was achieved in 33 of the 40 cadaveric digits (83%) with an A2 pulley laceration rate of 25%. No flexor tendon or neurovascular injuries occurred. Gross grasp, lateral pinch, 3-jaw chuck, and precision pinch strength had 85%, 90%, 82%, and 90% recovery, respectively. At the final follow-up, average metacarpophalangeal joint, proximal interphalangeal joint, and distal interphalangeal joint range of motion were within the normal limits. Mean VAS scores decreased from 5.7 preoperatively to 1.0 postoperatively and mean DASH score at the final follow-up was 4.8. Conclusions: With the use of anatomical surface landmarks, ETFR may be performed in an efficient and reproducible manner. Patients treated with ETFR had low complication rates, good functional recovery, and improved pain at short-term follow-up. Further study of long-term outcomes and cost-effectiveness of ETFR is warranted.
The corticostriatal circuit plays an important role in the regulation of reward- and aversion-types of behaviors. Specifically, the projection from the prelimbic cortex (PL) to the nucleus accumbens (NAc) has been shown to regulate sensory and affective aspects of pain in a number of rodent models. Previous studies have shown that enhancement of glutamate signaling through the NAc by AMPAkines, a class of agents that specifically potentiate the function of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, reduces acute and persistent pain. However, it is not known whether postsynaptic potentiation of the NAc with these agents can achieve the full anti-nociceptive effects of PL activation. Here we compared the impact of AMPAkine treatment in the NAc with optogenetic activation of the PL on pain behaviors in rats. We found that not only does AMPAkine treatment partially reconstitute the PL inhibition of sensory withdrawals, it fully occludes the effect of the PL on reducing the aversive component of pain. These results indicate that the NAc is likely one of the key targets for the PL, especially in the regulation of pain aversion. Furthermore, our results lend support for neuromodulation or pharmacological activation of the corticostriatal circuit as an important analgesic approach.
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