A Novel Ultrasound-Guided "Three in One" Approach Plus Interfascial Plane Blocks for the Treatment of Cervicogenic Headache.

Objective: Cervicogenic headache (CEH) is a condition resulting from upper cervical spine dysfunction and associated structural and soft tissue abnormalities, significantly impacting patients' quality of life. To acquire better therapeutic results, we presented a novel ultrasound-guided "three in one" approach plus interfascial plane (IFP) blocks for the treatment of CEH. This approach allows for the modulation of C2 dorsal root ganglion (DRG), third occipital nerve (TON), and C3 medial branch with one-point puncture. Additionally, it allows for IFP blocks between the upper neck and occipital muscles within the same scanning plane. Patients and Methods: We evaluated patients diagnosed with CEH from July 2021 to December 2022 in our pain clinic. We included those who did not respond to conservative treatment and single occipital nerve block, therefore received nerve block or pulsed radiofrequency (PRF) using the "Three in One" approach plus IFP blocks. The accuracy of the ultrasound-guided C2 DRG puncture procedures was confirmed through fluoroscopy with C-arm and the sensory testing of PRF. The therapeutic effect of these interventions was assessed using the numerical rating scale (NRS) scores during telephone follow-ups at 1, 3, and 6 months. Results: Utilizing the "Three in One" approach, a total of 5 patients diagnosed with CEH underwent nerve block plus IFP blocks, while 2 patients underwent PRF plus IFP blocks. Employing ultrasound-guided C2 DRG puncture procedures, the needle tip's correct placement was confirmed through both fluoroscopy and sensory testing of PRF. Notably, none of the cases experienced any complications associated with the approach. Subsequent follow-up assessments revealed an improvement in the NRS scores for CEH in all patients. Conclusion: The ultrasound-guided "Three in One" approach plus IFP blocks may be a potential effective method for the treatment of CEH.

The Utility of Peripherally Restricted Kappa-Opioid Receptor Agonists for Inhibiting Below-Level Pain After Spinal Cord Injury in Mice.

Pain after spinal cord injury (SCI) can be difficult to treat. Drugs that target the opioid receptor (OR) outside the central nervous system (CNS) have gained increasing interest in pain control owing to their low risk of central side effects. Asimadoline and ICI-204448 are believed to be peripherally restricted KOR agonists withlimited access to the CNS. This study examined whether they can attenuate pain hypersensitivity in mice subjected to a contusive T10 SCI. Subcutaneous (s.c.) injection of asimadoline (5, 20 mg/kg) and ICI-204448 (1, 10 mg/kg) inhibited heat hypersensitivity at both doses, but only attenuated mechanical hypersensitivity at the high dose. However, the high-dose asimadoline adversely affected animals' exploratory performance in SCI mice and caused aversion, suggesting CNS drug penetration. In contrast, high-dose ICI-204448 did not impair exploration and remained effective in reducing both mechanical and heat hypersensitivities after SCI. Accordingly, we chose to examine the potential peripheral neuronal mechanism for ICI-204448-induced pain inhibition by conducting in vivo calcium imaging of dorsal root ganglion (DRG) in Pirt-GCaMP6s+/- mice. High-dose ICI-204448 (10 mg/kg, s.c.) attenuated the increased fluorescence intensity of lumbar DRG neurons activated by a noxious pinch (400 g) stimulation in SCI mice. In conclusion, systemic administration of ICI-204448 achieved SCI pain inhibition at doses that did not induce notable side effects and attenuated DRG neuronal excitability which may partly contribute to its pain inhibition. These findings suggest that peripherally restricted KOR agonists may be useful for treating SCI pain, but the therapeutic window must be carefully examined.

The Preemptive Analgesic Effect of Capsaicin Involves Attenuations of Epidermal Keratinocytes Proliferation and Expression of Pro-Inflammatory Mediators After Plantar Incision in Rats.

Purpose: Subcutaneous infiltration of capsaicin, which initially activates transient receptor potential vanilloid 1 (TRPV1) receptors, can subsequently desensitize TRPV1-expressing nociceptors and induce analgesia in different pain models. Yet, whether the modulation of keratinocytes may also contribute to the analgesic action of capsaicin treatment remains unclear. In a rat model of postoperative pain, we tested the hypothesis that subcutaneous injection of capsaicin inhibited the proliferation of epidermal keratinocytes and their expression of pronociceptive inflammatory mediators after plantar incision. Methods: The plantar incision model was carried out in the current study. Behavioral tests were used to evaluate postoperative pain-related behaviors in rats. Immunohistochemistry was used to investigate epidermal keratinocytes proliferation and expression of pro-inflammatory mediators in keratinocytes in rats. Results: Behaviorally, plantar incision induced robust postoperative pain hypersensitivity. However, subcutaneous pretreatment of capsaicin (1%) but not the vehicle, prevented the development of postoperative pain. There was an increased proliferation of keratinocytes and the expressions of interleukin-1ß (IL-1ß) and tumour necrosis factor-alpha (TNF-α) in keratinocytes at 3 d and 7 d after plantar incision. However, these changes were also significantly attenuated by capsaicin pretreatment. Conclusion: Our findings suggest that capsaicin pretreatment may inhibit incision-induced keratinocytes proliferation and reduce their expression of pronociceptive inflammatory mediators under postoperative pain conditions, which represents a peripheral non-neuronal mechanism of capsaicin-induced analgesia.

Stellate ganglion block as an intervention in refractory eosinophilic granulomatosis with polyangiitis: a case report.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare vasculitis. Although glucocorticoid therapy with or without immunosuppressants leads to remission in the majority of cases, most EGPA patients remain dependent on glucocorticoid therapy and experience frequent relapses. Here, we report a case of refractory EGPA which responded to stellate ganglion blocks (SGBs). CASE PRESENTATION: A 32-year-old woman with aggravated wheezing, purpura, numbness of multiple fingers, and epigastric and abdominal pain was referred to our clinic. Laboratory and radiographic studies led to the diagnosis of EGPA. After an initial favorable response to glucocorticoid and immunosuppressant therapy, she experienced a relapse during a glucocorticoid taper. We found that SGB brought symptomatic relief and impeded disease progression. The mechanism of action of SGB on EGPA is undetermined, but may be related to vasodilation, immune modulation, and central nervous system regulation. CONCLUSIONS: This report not only proposes a novel treatment modality for EGPA, but also provides a clinical reference point for further in-depth studies of SGB in multiple immune-linked disorders.

Activation of CD200-CD200R1 Axis Attenuates Perioperative Neurocognitive Disorder Through Inhibition of Neuroinflammation in Mice.

Perioperative neurocognitive disorder (PND) is the mild cognitive impairment associated with surgery and anesthesia. It is a common surgical complication in the elderly. An important mechanism of PND is the surgically induced neuroinflammation. The interaction between the neuronal surface protein CD200 and its receptor in microglia, CD200R1, is an important regulatory pathway to control neuroinflammation. However, the potential role of the CD200-CD200R1 pathway in the acute period of PND has not been fully investigated. In this study, in a PND mouse model, we first measured the protein expression level of CD200, CD200R1, and the related pro- and anti-inflammatory cytokines in the hippocampus. Then, we investigated cognitive function, neuroinflammation and postsynaptic density protein 95 (PSD-95) expression after the injection of CD200-Fc (agonist), CD200R1-Fc (antagonist) or IgG1-Fc (vehicle) into lateral ventricle in PND models. Compared with the control group, the expression of CD200 was up-regulated at day 1 after surgery in PND models. The injection of the CD200-Fc into the lateral ventricle could mitigate primed neuroinflammation and cognitive decline, increase the expression of PSD-95 at day 1 after surgery in PND models. In conclusion, we have demonstrated that CD200-CD200R1 signaling was involved in the acute inflammatory process of PND, and activating CD200R1 can inhibit neuroinflammation and attenuate PND. Thus, the CD200-CD200R1 axis is a potential novel target for PND prevention and treatment.

Comparison of ultrasound-guided anterior quadratus lumborum block at the lateral supra-arcuate ligament with posterior quadratus lumborum block for perioperative analgesia in laparoscopic nephrectomy: a protocol for a randomised, prospective, parallel group, non-inferior trial.

OBJECTIVE: Anterior quadratus lumborum block at the lateral supra-arcuate ligament (QLBA) is a new method for postoperative pain relief in patients undergoing abdominal surgery. Perioperative QLBA is effective, but it has not been compared with posterior quadratus lumborum block (QLB2). The present study aims to evaluate the postoperative pain of patients undergoing laparoscopic nephrectomy surgery with QLBA versus QLB2. METHODS/DESIGN: This study is a randomised, prospective, parallel group, non-inferior trial. All patients undergoing laparoscopic nephrectomy surgery will be randomised 1:1 to the QLBA group or the QLB2 group with general anaesthesia. The objective of the trial is to evaluate the postoperative pain of patients undergoing laparoscopic nephrectomy surgery with QLBA (n=50) versus QLB2 (n=50). The primary outcome for this trial is the Visual Analogue Scale scores at rest and activity (dynamic pain scores are assessed with a cough or a trial to sit up in bed) 2 hours after surgery between patients who receive QLBA versus QLB2. The secondary objectives will be to compare (1) pain at rest and activity 0.5 hour, 2 hours, 24 hours, 48 hours after surgery; (2) the time spent on block operation; (3) the blocked dermatomal coverage 5 min and 15 min after block operation; (4) intraoperative opioid consumption; (5) types and doses of the rescue analgesic after surgery; (6) nausea and vomiting score within 24 hours after surgery; (7) time from the end of surgery to the first onset significant pain; (8) patient satisfaction score. DISCUSSION: Clinical experience has supported that QLB is a very effective postoperative analgesic method, and we will answer the following questions in this trial: Will both approaches have the same analgesic effect and duration? Will the QLBA have a non-inferior postoperative analgesic effect compared with QLB2 or the QLBA be able to prolong the duration of analgesia after surgery? The results of this study could have actual clinical applications that could help to reduce postoperative pain and shorten hospital stays. ETHICS AND DISSEMINATION: The study design was approved by the ethical committee of Beijing Chao-Yang Hospital, Beijing, China (2020-ke-321). The trial results will be published in peer-reviewed journals and at conferences. TRIAL REGISTRATION NUMBER: ChiCTR2000035354.

Cervical erector spinae plane block as a perioperative analgesia method for shoulder arthroscopy: a case series.

Shoulder arthroscopy, a common intervention for severe rotator cuff injuries, is associated with severe postoperative pain. Upon performing cervical erector spinae plane (ESP) blocks at the C7 TP (tip or posterior tip) or the posterior tip of the C6 TP posterior tubercle in six patients undergoing shoulder arthroscopy, sensory block was detectable in congruent cervico-thoracic dermatomes. Effective intraoperative and postoperative analgesia were consistently obtained for all six patients. This preliminary study illustrated that the cervical ESP block can be considered a potential simple regional anesthesia method for providing analgesia during shoulder arthroscopy with low risks of diaphragmatic paresis, upper extremity motor paresis, nerve injury and persistent hypotension.

Ultrasound-Guided Lumbar Paravertebral Block After Pre-Designed Route on X-Ray Film for Radicular Pain Following Failed Back Surgery Syndrome: A Case Report.

BACKGROUND: Persistent or recurring radicular pain after lumbar surgery is a clinical condition of failed back surgery syndrome (FBSS) that seriously affects the life quality of patients. Conventional medication and physiotherapy do not fully relieve this pain. A simpler, safer, and less invasive option is lumbar selective nerve root block or paravertebral block. Here, we share our experience regarding lumbar paravertebral block for a patient with FBSS, which successfully alleviated radicular pain after lumbar surgery. CASE PRESENTATION: An 80-year-old man with left lower limb radicular pain diagnosed as L4-5, L5-S1 intervertebral disc protrusion, spinal canal stenosis, and degenerative scoliosis underwent lumbar surgery. Four months after surgery, he experienced left lower limb radicular pain. After designing the puncture route based on X-ray film, we performed a combined ultrasound-guided L4 and L5 paravertebral block. With his improved pain control, his functional status and ability to perform daily activities also markedly improved. CONCLUSION: Real-time ultrasound-guided lumbar paravertebral block performed with a pre-designed route on X-ray film can provide a simple and safe way to relieve radicular pain in FBSS.

A Case Report of an Ultrasound-Guided and Fluoroscopy-Assisted Posterior Approach for Celiac Plexus Neurolysis in a Patient with Pancreatic Cancer-Associated Abdominal Pain.

BACKGROUND: Imaging-guided celiac plexus neurolysis using ultrasound (US) guidance via a transabdominal approach and endoscopic-ultrasound (EUS) has been increasingly applied for the treatment of pancreatic cancer-associated abdominal pain. OBJECTIVE: To investigate the application of ultrasound-guided and fluoroscopy-assisted celiac plexus neurolysis in a patient with advanced pancreatic cancer suffering from refractory abdominal pain for which oral opioid treatment was ineffective. CASE REPORT: We report a case of ultrasound-guided and fluoroscopy-assisted celiac plexus neurolysis in a patient with advanced pancreatic cancer with refractory abdominal pain. With the patient in the prone position, celiac plexus neurolysis was performed under real-time US guidance. The transducer was placed below the costal margin and a puncture needle with an ultrasound enhancement tip was inserted in-plane aiming for the lateral anterior end of the vertebral body. The correct needle tip position was confirmed by the C-arm with contrast material located anterior to the vertebral body and posterior to the diaphragm. CONCLUSION: We highlight the use of an US-guided and fluoroscopy-assisted posterior approach for use in celiac plexus neurolysis procedures, particularly in patients suffering from contraindications from the US or EUS-guided anterior approaches.

Atorvastatin protects against postoperative neurocognitive disorder via a peroxisome proliferator-activated receptor-gamma signaling pathway in mice.

OBJECTIVE: Postoperative neurocognitive disorder (PND) is a main complication that is commonly seen postoperatively in elderly patients. The underlying mechanism remains unclear, although neuroinflammation has been increasingly observed in PND. Atorvastatin is a pleiotropic agent with proven anti-inflammatory effects. In this study, we investigated the effects of atorvastatin on a PND mouse model after peripheral surgery. MATERIAL AND METHODS: The mice were randomized into five groups. The PND models were established, and an open field test and fear condition test were performed. Hippocampal inflammatory cytokine expression was determined using ELISA. Peroxisome proliferator-activated receptor-gamma (PPARγ) expression in the hippocampus was tested using qRT-PCR and western blot analysis. RESULTS: On day 1 after surgery, inflammatory cytokines such as tumor necrosis factor-α, interleukin-1ß, and interleukin-6 showed a significant increase in the hippocampus, with prominent cognitive impairment. Atorvastatin treatment improved cognitive function in the mouse model, attenuated neuroinflammation, and increased PPARγ expression in the hippocampus. However, treatment with the PPARγ antagonist GW9662 partially reversed the protective effects of atorvastatin. CONCLUSIONS: These results indicated that atorvastatin improves several hippocampal functions and alleviates inflammation in PND mice after surgery, probably through a PPARγ-involved signaling pathway.

Persistent proliferation of keratinocytes and prolonged expression of pronociceptive inflammatory mediators might be associated with the postoperative pain in KK mice.

Epidermal keratinocytes play a vital role in restoration of the intact skin barrier during wound healing. The negative effect of hyperglycemia may prolong the wound healing process. Epidermal keratinocytes have been demonstrated to modulate and directly initiate nociceptive responses in rat models of fractures and chemotherapy-induced neuropathic pain. However, it is unclear whether epidermal keratinocytes are involved in the development and maintenance of incisional pain in nondiabetic or diabetic animals. In the current study, using behavioral tests and immunohistochemistry, we investigated the differential keratinocytes proliferation and expression of pronociceptive inflammatory mediators in keratinocytes in C57BL/6J mice and diabetic KK mice. Our data showed that plantar incision induced postoperative pain hypersensitivity in both C57BL/6J mice and KK mice, while the duration of postoperative pain hypersensitivity in KK mice was longer than that in C57BL/6J mice. Moreover, plantar incision induced the keratinocytes proliferation and expression of IL-1ß and TNF-α in keratinocytes in both C57BL/6J mice and KK mice. Interestingly, compared to C57BL/6J mice, the slower and more persistent proliferation of keratinocytes and expression of IL-1ß and TNF-α in keratinocytes were observed in KK mice. Together, our study suggested that plantar incision may induce the differential keratinocytes proliferation and expression of IL-1ß and TNF-α in kertinocytes in diabetic and nondiabetic animals, which might be associated with the development and maintenance differences in diabetic and nondiabetic postoperative pain.

Feasibility of ultrasound-guided lumbar epidural access using paramedian transverse scanning with the needle in-plane: a comparison with paramedian sagittal scanning.

BACKGROUND AND OBJECTIVES: The present study was designed to compare the feasibility of ultrasound (US)-guided lumbar epidural access using paramedian sagittal scanning (PMSS) and paramedian transverse scanning (PMTS) approaches. METHODS: Fifty patients undergoing surgery of the lower extremities were randomly allocated into 2 groups. The patients in PMSS group received PMSS-guided in-plane epidural access, whereas patients in PMTS group received PMTS-guided in-plane epidural access. The US visibility of neuraxial structures and of Tuohy needle during US scout scan, procedure duration, the number of attempts to access epidural space, Tuohy needle puncture depth in the epidural space, and extent of sensory block after spinal block between two groups were compared. RESULTS: The US visibility of Tuohy needle and neuraxial structures was comparable between two groups. There was an overall decrease in procedure duration in the PMTS group relative to the PMSS group (360 ± 42 vs. 490 ± 38 s). The number of attempts needed to access the epidural space in PMSS group was significantly higher than in PMTS group. Distances between the epidural space and the puncture site in PMSS group and PMTS group showed a significant difference (7.13 ± 0.67 vs. 5.24 ± 0.21 cm). No significant differences in the extent of sensory block after spinal block were observed. CONCLUSIONS: We found that PMTS approach was superior as a means of achieving epidural access relative to the PMSS approach, since PMTS approach can be conducted more quickly given shorter path of the needle and less times needed for epidural access during this procedure. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, clinical trial number ChiCTR1800015815, date of registration April 24, 2018.

Upregulation of spinal glucose-dependent insulinotropic polypeptide receptor induces membrane translocation of PKCγ and synaptic target of AMPA receptor GluR1 subunits in dorsal horns in a rat model of incisional pain.

It is unclear whether glucose-dependent insulinotropic polypeptide receptor (GIPR) signaling plays an important role in spinal nociception. We hypothesized that the spinal GIPR is implicated in central sensitization of postoperative pain. Our data showed that the cumulative pain scores peaked at 3 h, kept at a high level at 1 d after incision, gradually decreased afterwards and returned to the baseline values at 5 d after incision. Correspondingly, the expression of GIPR in spinal cord dorsal horn peaked at 1 d after incision, and returned to the baseline value at 5 d after incision. The double-labeling immunofluorescence demonstrated that spinal GIPR was expressed in dorsal horn neurons, but not in astrocyte or microglial cells. At 1 d after incision, the effects of intrathecal saline, GIPR antagonist (Pro3)GIP on pain behaviors were investigated. Our data showed that at 30 min and 60 min following intrathecal treatments of 300 ng (Pro3)GIP, the cumulative pain scores were decreased and paw withdrawal thresholds to mechanical stimuli were increased when compared to those immediately before intrathecal treatments. Accordingly, at 30 min after intrathecal injections, the membrane translocation levels of PKCγ and the GluR1 expression in postsynaptic membrane in ipsilateral dorsal horns to the incision were significantly upregulated in rats with intrathecal saline injections, as compared to normal control group. At 30 min after intrathecal treatment, (Pro3)GIP inhibited the membrane translocation levels of PKCγ and the GluR1 expression in postsynaptic membrane in ipsilateral dorsal horns. Our study indicates that upregulation of spinal GIPR may contribute to pain hypersensitivity through inducing membrane translocation level of PKCγ and synaptic target of AMPA receptor GluR1 subunits in ipsilateral dorsal horns of rats with plantar incision.

Dermorphin [D-Arg2, Lys4] (1-4) amide inhibits below-level heat hypersensitivity in mice after contusive thoracic spinal cord injury.

Opioid use for chronic pain is limited by severe central adverse effects. We examined whether activating mu-opioid receptors (MORs) in the peripheral nervous system attenuates spinal cord injury (SCI) pain-like behavior in mice. We produced a contusive SCI at the T10 vertebral level and examined motor and sensory dysfunction for 6 weeks. At 6 weeks, we tested the effect of subcutaneous (s.c.) injection of dermorphin [D-Arg2, Lys4] (1-4) amide (DALDA), a peripherally acting MOR-preferring agonist, on mechanical and heat hypersensitivity. Basso mouse scale score was significantly decreased after SCI, and mice showed hypersensitivity to mechanical and heat stimulation at the hind paw beginning at 2 weeks, as indicated by increased paw withdrawal frequency to mechanical stimulation and decreased paw withdrawal latency to heat stimulation. In wild-type SCI mice, DALDA (1 mg/kg, s.c.) attenuated heat but not mechanical hypersensitivity. The effect was blocked by pretreatment with an intraperitoneal injection of methylnaltrexone (5 mg/kg), a peripherally restricted opioid receptor antagonist, and was also diminished in Pirt-MOR conditional knockout mice. DALDA did not adversely affect exploratory activity or induced preference to drug treatment in SCI mice. In vivo calcium imaging showed that DALDA (1, 10 mg/kg, s.c.) inhibited responses of small dorsal root ganglion neurons to noxious heat stimulation in Pirt-GCaMP6s mice after SCI. Western blot analysis showed upregulation of MOR in the lumbar spinal cord and sciatic nerves at 6 weeks after SCI. Our findings suggest that peripherally acting MOR agonist may inhibit heat hypersensitivity below the injury level with minimal adverse effects.

Videolaryngoscopy versus direct laryngoscopy for nasotracheal intubation: A systematic review and meta-analysis of randomised controlled trials.

STUDY OBJECTIVE: Nasotracheal intubation (NTI) is a common practice in the oral and maxillofacial surgeries. A systematic review and meta-analysis was performed to determine whether videolaryngoscopy (VL) compared with direct laryngoscopy (DL) can lead to better outcomes for NTI in adult surgical patients. MEASUREMENTS: Only randomised controlled trials comparing VL and DL for NTI were included. The primary outcome was overall success rate and the second outcomes were first-attempt success rate, intubation time, rate of Cormack and Lehane classification 1, rate of Magill Forceps used, rate of postoperative sore throat, and ease of intubation. MAIN RESULTS: Fourteen studies with 20 comparisons (n = 1052) were included in quantitative synthesis. The overall success rate was similar between two groups (RR, 1.03; p = 0.14; moderate-quality evidence). VL was associated with a higher first-attempt success rate (RR 1.09; p = 0.04; low-quality evidence), a shorten intubation time (MD-6.72 s; p = 0.0001; low-quality evidence), a higher rate of Cormack and Lehane classification 1 (RR, 2.11; p < 0.01; high-quality evidence), a less use of the Magill forceps (RR, 0.11; p < 0.01; high-quality evidence) and a lower incidence of postoperative sore throat (RR, 0.50; p = 0.03; high-quality evidence). Subgroup analysis based on whether with a difficult airway showed higher overall success (p < 0.01) and first-attempt success rates with VL (p = 0.04) in patients with difficult airways; however, these benefits was not shown in patients with a normal airway (p > 0.05); Subgroup analysis based on operators' experience showed that success rate did not differ between groups (p > 0.05), but intubation time was shortened by more than 50s by non-experienced operators (p < 0.05). Subgroup analysis based on different devices used showed that only non-integrated VL led to a shorter intubation time (p < 0.05). CONCLUSIONS: The use of VL does not increase the overall success rate of NTI in adult patients with general anesthesia, but it improves the first-attempt success rate and laryngeal visualization, and shortens the intubation time. VL is particularly beneficial for patients with difficult airways.

Paradoxical Sleep Deprivation Aggravates and Prolongs Incision-Induced Pain Hypersensitivity via BDNF Signaling-Mediated Descending Facilitation in Rats.

The mechanisms underlying the pronociceptive effect of paradoxical sleep deprivation (PSD) are not fully established. The modulation of BDNF signaling-mediated descending facilitation from the rostral ventromedial medulla (RVM) of brain stem has been demonstrated in persistent pain models of inflammatory pain, but not in incisional pain model. Recent study has shown that PSD increases the expression of brain-derived neurotrophic factor (BDNF) in the brainstem structure. Therefore, in the current study, we asked whether the BDNF signaling-mediated descending facilitation was involved in the PSD-induced pronociceptive effect on incisional pain and delay the recovery period of postoperative pain in rats. Our results found that a preoperative 24 h PSD significantly aggravated the pain hypersensitivity after incision and prolonged the duration of postoperative pain. The lesions of ipsilateral dorsolateral funiculus partly reversed the PSD-induced pronociceptive effect on incisional pain. Interestingly, the 24 h PSD, but not incision significantly enhanced the levels of BDNF protein expression in the RVM areas of rats. Furthermore, at 1 day or 4 days after incision, intra-RVM microinjection of a BDNF antibody partly reversed the PSD-induced pronociceptive effects in incisional rats, while it did not change the cumulative pain scores and paw withdrawal thresholds in rats receiving only plantar incision. These findings suggest that the preoperative PSD may aggravate and prolong the incision-induced pain hypersensitivity via BDNF signaling-mediated descending facilitation.

Increased Neuroligin 2 Levels in the Postsynaptic Membrane in Spinal Dorsal Horn may Contribute to Postoperative Pain.

Neuroligin 2 is a synaptic cell adhesion molecule that is mainly located in inhibitory synapses and is crucial in the regulation of synapse function through protein-protein interactions. However, researchers have not clearly determined whether neuroligin 2 is involved in the development of postoperative pain. In the current study, Western blot, immunofluorescence staining and co-immunoprecipitation were used to examine the critical role of neuroligin 2 in postoperative pain hypersensitivity. A small interfering ribonucleic acid (siRNA)-targeting neuroligin 2 was used to inhibit neuroligin 2 expression. Our data found that plantar incision induced postoperative pain hypersensitivity, which was characterized by paw withdrawal threshold and cumulative pain score. The upregulation of neuroligin 2 and GluR1 expression in the postsynaptic membranes of ipsilateral spinal dorsal horn was observed at 3 h and 1 day after plantar incision. Additionally, at 3 h after plantar incision, the amount of PSD-95 that was co-immunoprecipitated with neuroligin 2 antibody was significantly increased in the ipsilateral dorsal horn, as compared to that of the control group. Intrathecal pretreatment of siRNA-targeting neuroligin 2 to reduce the neuroligin 2 expression in the spinal cord significantly inhibited the pain hypersensitivity and reduced the synaptic targeting of GluR1 in ipsilateral dorsal horns. Our study indicates that the incision-induced interaction between neuroligin 2 and PSD-95 and subsequent synaptic targeting of GluR1 in ipsilateral dorsal horns contribute to postoperative pain hypersensitivity.