YokoCo

Emergence Delirium (ED) is an essential condition in the immediate postoperative period. Systematic review and meta-analysis of randomized controlled trials have concluded that the effect of ketamine on postoperative delirium remains unclear. The present study sought to evaluate if the intraoperative use of ketamine for postoperative analgesia is associated with postoperative ED in laparoscopic surgeries.

Opioids are among the most effective analgesics for the management of pain in the acute phase of a spinal cord injury (SCI), and approximately 80% of patients are treated with morphine in the first 24 h following SCI. We have found that morphine treatment in the first 7 days after SCI increases symptoms of pain at 42 days post-injury and undermines the recovery of locomotor function in a rodent model. Prior research has implicated microglia/macrophages in opioid-induced hyperalgesia and the development of neuropathic pain. We hypothesized that glial activation may also underlie the development of morphine-induced pain and cell death after SCI. Supporting this hypothesis, our previous studies found that intrathecal and intravenous morphine increase the number of activated microglia and macrophages present at the spinal lesion site, and that the adverse effects of intrathecal morphine can be blocked with intrathecal minocycline. Recognizing that the cellular expression of opioid receptors, and the intracellular signaling pathways engaged, can change with repeated administration of opioids, the current study tested whether minocycline was also protective with repeated intravenous morphine administration, more closely simulating clinical treatment. Using a rat model of SCI, we co-administered intravenous morphine and intrathecal minocycline for the first 7 days post injury and monitored sensory and locomotor recovery. Contrary to our hypothesis and previous findings with intrathecal morphine, we found that minocycline did not prevent the negative effects of morphine. Surprisingly, we also found that intrathecal minocycline alone is detrimental for locomotor recovery after SCI. Using ex vivo cell cultures, we investigated how minocycline and morphine altered microglia/macrophage function. Commensurate with published studies, we found that minocycline blocked the effects of morphine on the release of pro-inflammatory cytokines but, like morphine, it increased glial phagocytosis. While phagocytosis is critical for the removal of cellular and extracellular debris at the spinal injury site, increased phagocytosis after injury has been linked to the clearance of stressed but viable neurons and protracted inflammation. In sum, our data suggest that both morphine and minocycline alter the acute immune response, and reduce locomotor recovery after SCI.

Because of the fear of the use of pharmacological agents, many pregnant women are opting to use alternative management modalities either as primary management or to compliment standard contemporary medical practices. The traditional complementary physical interventions of acupuncture, acupressure, and electrostimulation have a long tradition of use in traditional Chinese medical practice and are advocated for the management of antenatal conditions such as spontaneous miscarriages, gastrointestinal, respiratory, and urinary problems. They have also been advocated as useful to help the process of labour in promoting a cephalic delivery, induction/augmentation of labour and pain relief. Postpartum these modalities have been said to help the secretion and production of milk. While a number of studies, some randomized controlled, have suggested a potential role for these traditional complementary physical interventions, systematic reviews have generally failed to show a definite conclusive beneficial role and all reviews generally suggest the need for further controlled research in the field. Since no adverse effects appear to be associated with the use of these modalities in pregnancy, such modalities of management can be considered but only as an adjuvant to standard pharmacological management after a full clinical assessment has ruled out underlying pathology.

Nerve injury-induced neuropathic pain is a type of chronic pain associated with neuroinflammatory response and neuronal death; however the underlying molecular mechanisms are still unclear. Dual-specificity phosphatase 8 (DUSP8) can mediate numerous cellular events, but whether it's involved in neuropathic pain is unknown. In the study, we found that spinal nerve ligation (SNL) operation on rats significantly decreased DUSP8 expression levels in ipsilateral spinal cord (ISC) tissues. Consistently, lipopolysaccharide (LPS) exposure also reduced DUSP8 in murine microglial cells. Adeno-associated virus (AAV)-mediated DUSP8 over-expression was found to considerably ameliorate SNL-induced neuropathic pain in rats. Additionally, neuronal death in the ISC tissues was also attenuated by AAV-DUSP8 following SNL surgery. Moreover, SNL-triggered neuroinflammation and microglial activation were also mitigated upon DUSP8 over-expression by suppressing nuclear factor κB (NF-κB) signaling, which were validated in LPS-exposed microglial cells. Importantly, our in vitro experiments indicated that inflammatory response in microglial cells contributed to neuron death, and such effect could also be ameliorated by DUSP8 over-expression. Notably, we found that DUSP8 directly interacted with transforming growth factor β activated kinase-1 (TAK1) in microglial cells. Both SNL and LPS led to the activation of TAK1/p38/JNK1/2 signaling, whereas being strongly abolished by DUSP8. Intriguingly, TAK1 blockage significantly diminished LPS-induced inflammation and neuron death, whereas being accelerated by DUSP8 knockdown, further indicating that DUSP8-ameliorated neuropathic pain was largely TAK1-dependent. Together, all our findings revealed that DUSP8/TAK1 signaling may be a potential target for neuropathic pain alleviation.

This study aimed to explore the changes in gamma-aminobutyric acid (GABA) and glutamate (Glu) levels, and their correlations with clinical indicators in patients with postherpetic neuralgia (PHN).

Acute pain after mastectomy is increased with concurrent breast reconstruction. One postulated advantage of prepectoral breast reconstruction is less postoperative pain; however, no comparisons to partial submuscular reconstruction have been made to date. Here, we examined the postoperative pain experienced between patients with prepectoral and subpectoral breast reconstruction after mastectomy.

The bladder wall is innervated by a complex network of afferent nerves that detect bladder stretch during filling. Sensory signals, generated in response to distension, are relayed to the spinal cord and brain to evoke physiological and painful sensations and regulate urine storage and voiding. Hyperexcitability of these sensory pathways is a key component in the development of chronic bladder hypersensitivity disorders including interstitial cystitis/bladder pain syndrome and overactive bladder syndrome. Despite this, the full array of ion channels that regulate bladder afferent responses to mechanical stimuli have yet to be determined. Here we investigated the role of low-voltage activated T-type calcium (CaV3) channels in regulating bladder afferent responses to distension. Using single-cell reverse-transcription polymerase chain reaction and immunofluorescence we revealed ubiquitous expression of CaV3.2, but not CaV3.1 or CaV3.3 in individual bladder-innervating dorsal root ganglia (DRG) neurons. In an ex vivo bladder-nerve recording preparation pharmacological inhibition of CaV3.2 with TTA-A2 and ABT-639, selective blockers of T-type calcium channels, dose-dependently attenuated bladder afferent responses to distension in the absence of changes to muscle compliance. Further evaluation revealed CaV3.2 blockers significantly inhibited both low- and high-threshold afferents, decreasing peak responses to distension, and delaying activation thresholds, thereby attenuating bladder afferent responses to both physiological and noxious distension. Nocifensive visceromotor responses to noxious bladder distension in-vivo were also significantly reduced by inhibition of CaV3 with TTA-A2. Together these data provide evidence of a major role for CaV3.2 in regulating bladder afferent responses to bladder distension and nociceptive signalling to the spinal cord.

Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a common and debilitating disease with poor treatment outcomes. Studies from the Multidisciplinary Approach to the study of chronic Pelvic Pain (MAPP) research network established that IC/BPS patients with chronic overlapping pain conditions (COPCs) experience poorer quality of life and more severe symptoms, yet the neurobiological correlates of this subtype are largely unknown. We previously showed that ex-vivo Toll-Like Receptor 4 (TLR4) cytokine/chemokine release is associated with the presence of COPCs, as well as widespread pain and experimental pain sensitivity women with IC/BPS. Here we attempt to confirm these findings in the multisite MAPP Symptom Patterns Study using TLR4 stimulated whole blood (female IC/BPS patients with COPC n =99; without n=36). Samples were collected in tubes preloaded with TLR4 agonist, incubated for 24 hours, and resulting supernatant assayed for seven cytokines/chemokines. These were subject to a principal components analysis and the resulting components used as dependent variables in general linear models. Controlling for patient age, body mass index, and site of collection, we found that greater ex-vivo TLR4 stimulated cytokine/chemokine release was associated with the presence of COPCs (p < 0.01), extent of widespread pain (p < 0.05), but not experimental pain sensitivity (p > 0.05). However, a second component of anti-inflammatory, regulatory, and chemotactic activity was associated with reduced pain sensitivity (p < 0.01). These results confirm that the IC/BPS + COPCs subtype show higher levels of ex-vivo TLR4 cytokine/chemokine release and support a link between immune priming and nociplastic pain in IC/BPS.

Spina bifida (SB) is caused by a failure in neural tube closure that can present with lower extremity sensory deficits, paralysis, and hydrocephalus. Medical advances have allowed increased pregnancies among SB patients, but management and pregnancy-associated complications have not been thoroughly investigated. The objective is to delineate peripartum procedures and complications in patients with SB.

An 89-year-old woman presented with chronic pain and foreign body sensation in a healthy-appearing anophthalmic socket. Computed tomography of the orbits showed hyperdense, cystic lesions superior and posterior to the orbital implant. Orbital exploration was performed; the orbital implant and lesions were removed. Histopathology revealed cystic structures composed of fibrocellular tissue lined with histiocytes and multinucleated giant cells, consistent with pseudocysts. Postoperatively, the patient noted the resolution of her symptoms. While the etiology of the pseudocysts remains unclear, we hypothesize that the answer can be traced back to the original surgery. The cysts may have formed after extravasation of fluid or proteinaceous material from the eye, from glycerin on the donor sclera, or after introduction of foreign material during retrobulbar injection of local anesthesia. This is the first report of pseudocysts occurring in the orbit posterior to an implant.