Rejected

Gastrin-releasing peptide (GRP) and its receptor (GRPR) have been identified as itch mediators in the spinal and trigeminal somatosensory systems in rodents. In primates, there are few reports of GRP/GRPR expression or function in the spinal sensory system and virtually nothing is known in the trigeminal system. The aim of the present study was to characterize GRP and GRPR in the trigeminal and spinal somatosensory system of Japanese macaque monkeys (Macaca fuscata). cDNA encoding GRP was isolated from the macaque dorsal root ganglion (DRG) and exhibited an amino acid sequence that was highly conserved among mammals and especially in primates. Immunohistochemical analysis demonstrated that GRP was expressed mainly in the small-sized trigeminal ganglion and DRG in adult macaque monkeys. Densely stained GRP-immunoreactive (ir) fibers were observed in superficial layers of the spinal trigeminal nucleus caudalis (Sp5C) and the spinal cord. In contrast, GRP-ir fibers were rarely observed in the principal sensory trigeminal nucleus and oral and interpolar divisions of the spinal trigeminal nucleus. cDNA cloning, in situ hybridization, and Western blot revealed substantial expression of GRPR mRNA and GRPR protein in the macaque spinal dorsal horn and Sp5C. Our Western ligand blot and ligand derivative stain for GRPR revealed that GRP directly bound in the macaque Sp5C and spinal dorsal horn as reported in rodents. Finally, GRP-ir fibers were also detected in the human spinal dorsal horn. The spinal and trigeminal itch neural circuits labeled with GRP and GRPR appear to function also in primates.

To explore how patients who participate in an interdisciplinary pain rehabilitation program (IPRP) experience a three-party meeting based on the Demand and Ability Protocol (DAP) to assist in return to work (RTW). The DAP is a employee and his/her immediate manager under the guidance of medical staff with knowledge of the patient's work requirements and his/her current functional ability.

Incidental, asymptomatic pituitary adenomas require nuanced, shared decision-making, which is limited by a poor understanding of their natural history and effects on quality of life (QOL). A greater understanding of the effects of surgery would inform evidence-based care.

Although it has been established that adolescent idiopathic cervical kyphosis (AICK) has no known cause, there are associated risk factors. However, the underlying causes remain puzzling. This case report presents severe AICK linked to chronic neck flexion postural habit, treated with combined anterior and posterior correction surgery and review of the literature.

The prevalence of abuse, diversion, and web-based endorsement of tapentadol (extended-release [ER], immediate-release [IR]) has been characterized as low compared with other prescription opioids. Little is known about individual experience with tapentadol nonmedical use (NMU).

Neuropathic pain (NP) is a common chronic condition that severely affects patients with spinal cord injuries (SCI). It impairs the overall quality of life and is considered difficult to treat. Currently, clinical management of NP is often limited to drug therapy, primarily with opioid analgesics that have limited therapeutic efficacy. The persistence and intractability of NP following SCI and the potential health risks associated with opioids necessitate improved treatment approaches. Nanomedicine has gained increasing attention in recent years for its potential to improve therapeutic efficacy while minimizing toxicity by providing sensitive and targeted treatments that overcome the limitations of conventional pain medications. The current perspective begins with a brief discussion of the pathophysiological mechanisms underlying NP and the current pain treatment for SCI. We discuss the most frequently used nanomaterials in pain diagnosis and treatment as well as recent and ongoing efforts to effectively treat pain by proactively mediating pain signals following SCI. Although nanomedicine is a rapidly growing field, its application to NP in SCI is still limited. Therefore, additional work is required to improve the current treatment of NP following SCI.

Maternity statistics of England in 2020 showed rise in Caesarean Section (CS) rate to 31%. Some studies correlated adverse gynaecological symptoms e.g. menstrual irregularities and pelvic pain to 'niche' formation at CS scar site. Niche formation was speculated to cause myometrial hypertrophy aggravating these symptoms. This was a prospective comparative histological study including 52 consecutive benign hysterectomy specimens which were categorised into 2 groups: (i) specimens with CS scar ( = 22), (ii) specimens with no CS scar ( = 30). Median (IQ range) uteri weight was 97.2grms (43.5-226) and 91.7grms (35.7-201.7) in study and control groups, respectively ( = .991). Mean (±SD) thickness of anterior myometrial wall was 18.7 mm (±3.6) and 19.4 mm (±4.5) in study and control groups, respectively ( = .58). Mean (±SD) thickness of posterior myometrial wall was 19.1 mm (±3.7) and 18.7 mm (±3.9) in study and control groups, respectively ( = .78). The assumption that CS scar causes myometrial hypertrophy was not demonstrated in this study.IMPACT STATEMENT Maternity statistics world-wide show a continuous rise in the rate of Caesarean Section (CS) operation. The CS scar is assumed to be related to adverse clinical gynaecological symptoms such as intermenstrual bleeding, dysmenorrhoea, dyspareunia and chronic pelvic pain; however, the mechanism of this association is not clear. Further, little is known about the effects of CS scar on uterine wall morphology and function. This study was the first prospective series in the literature to compare the uteri with scar with those without in respect of weight and myometrial wall thickness. It was not able to demonstrate the association between having CS scar and myometrial hypertrophy which was hypothesised to be the cause of adverse gynaecological symptoms. However, the microscopic examination of the CS scar revealed adenomyosis, haemorrhage and/or chronic inflammation in most cases. The clinical implication of the histological changes shown in the CS scar requires large comparative clinical studies.

Peripheral nerve block (PNB) for patients with total knee arthroplasty (TKA) is one of the recommended interventions in ERAS protocols. However, most existing studies involved unilateral TKA (UTKA). As such, this study aimed to evaluate the effectiveness of PNB in terms of immediate postoperative analgesia, length of hospital stays (LOS), and early functional outcomes in both UTKA and simultaneous bilateral TKAs (BTKAs). We reviewed 236 patients who underwent primary TKA with PNB, with 138 and 98 being UTKA and BTKAs, respectively; those in the PNB group underwent femoral nerve and adductor canal block. The matched control and PNB groups-who received intravenous/epidural patient-controlled analgesia (IVPCA/PCEA) alone or IVPCA in addition to PNB after surgery, respectively-were compared. The VAS scores at rest until 48 h after surgery were significantly lower in PNB groups compared to those in the IVPCA groups. At 0- 6 h of activity, VAS scores of the UTKA with PNB group were also lower than the IVPCA group. Compared to PCEA groups, VAS scores at 0-6 h of activity were higher in both the UTKA and BTKAs with PNB groups. However, at 24-48 h at rest, the scores of those in the UTKA with PNB group were lower than those in the PCEA group. The control and experimental UTKA and BTKAs groups had similar LOS and functional outcomes at 90 days postoperatively. In primary TKA, PNB has great analgesic effects for immediate postoperative pain control, and represents a similar analgesic effect to epidural PCA.

Celecoxib-tramadol co-crystal (CTC) is a first-in-class analgesic co-crystal of celecoxib and racemic tramadol with an improved pharmacologic profile, conferred by the co-crystal structure, compared with its active constituents administered alone/concomitantly. We evaluated CTC in moderate-to-severe acute postoperative pain. This randomized, double-blind, factorial, active- and placebo-controlled phase 3 trial (NCT03108482) was conducted at 6 US clinical research centers. Adults with moderate-to-severe acute pain following bunionectomy with osteotomy were randomized to oral CTC (200 mg [112 mg celecoxib/88 mg rac-tramadol hydrochloride] every 12 hours), tramadol (50 mg every 6 hours), celecoxib (100 mg every 12 hours), or placebo for 48 hours. Patients, investigators, and personnel were blinded to assignment. The primary endpoint was the 0-48h sum of pain intensity differences (SPID ) in all randomized patients. Pain intensity was assessed on a 0-10 numerical rating scale (NRS). Safety was analyzed in patients who received study medication. Funded by ESTEVE Pharmaceuticals. In 2017 (March to November), 1323 patients were screened and 637 randomized to CTC (n=184), tramadol (n=183), celecoxib (n=181), or placebo (n=89). Mean baseline NRS was 6.7 in all active groups. CTC had a significantly greater effect on SPID (least-squares mean: -139.1 [95% confidence interval: -151.8, -126.5]) than tramadol (-109.1 [-121.7, -96.4]; P<0.001), celecoxib (-103.7 [-116.4, -91.0]; P<0.001), or placebo (-74.6 [-92.5, -56.6]; P<0.001). Total treatment-emergent adverse events (TEAEs) were 358 for CTC and 394 for tramadol. Drug-related TEAEs occurred in 37.7% patients in the CTC group, compared with 48.6% in the tramadol group. There were no serious TEAEs/deaths. CTC provided greater analgesia than comparable daily doses of tramadol and celecoxib, with similar tolerability to tramadol. CTC is approved in the US.