BackgroundPyruvate kinase isozymes M2 (PKM2), as a member of pyruvate kinase family, plays a role of glycolytic enzyme in glucose metabolism. It also functions as protein kinase in cell proliferation, signaling, immunity, and gene transcription. In this study, the role of PKM2 in neuropathic pain induced by chronic constriction injury (CCI) was investigated.MethodsRats were randomly grouped to establish CCI models. PKM2, extracellular regulated protein kinases (EKR), p-ERK, signal transducers and activators of transcription (STAT3), p-STAT3, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and p-PI3K/AKT proteins expression in spinal cord was examined by Western blot analysis. Cellular location of PKM2 was examined by immunofluorescence. Knockdown of PKM2 was achieved by intrathecal injection of specific small interfering RNA (siRNA). Von Frey filaments and radiant heat tests were performed to determine mechanical allodynia and thermal hyperalgesia respectively. Lactate and adenosine triphosphate (ATP) contents were measured by specific kits. Tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels were detected by ELISA kits.ResultsCCI markedly increased PKM2 level in rat spinal cord. Double immunofluorescent staining showed that PKM2 co-localized with neuron, astrocyte, and microglia. Intrathecal injection of PKM2 siRNA not only attenuated CCI-induced ERK and STAT3 activation, but also attenuated mechanical allodynia and thermal hyperalgesia induced by CCI. However, PKM2 siRNA failed to inhibit the activation of AKT. In addition, PKM2 siRNA significantly suppressed the production of lactate and pro-inflammatory mediators.ConclusionOur findings demonstrate that inhibiting PKM2 expression effectively attenuates CCI-induced neuropathic pain and inflammatory responses in rats, possibly through regulating ERK and STAT3 signaling pathway.

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The development of digital oedema, adhesion formation, and resistance to digital motion at days 0, 3, 5, 7, 9 and 14 after primary flexor tendon repairs using 102 long toes of 51 Leghorn chickens was studied. Oedema presented as tissue swelling from days 3 to 7, which peaked at day 3. After day 7, oedema was manifest as hardening of subcutaneous tissue. The degree of digital swelling correlated with the resistance to tendon motion between days 3 and 7. At day 9, granulation tissues were observed around the tendon and loose adhesions were observed at day 14. Resistance to digital motion increased significantly from day 0 to day 3, but did not increase between days 3 and 9. The early postoperative changes appear to have three stages: initial (days 0-3, increasing resistance with development of oedema), delayed (days 4-7, higher resistance with continuing oedema) and late (after day 7-9, hardening of subcutaneous tissue with development of adhesions).

Objective To observe whether ultrasound-guided stellate ganglion block (SGB) can effectively relieve migraine pain and improve the quality of migraine patients’ life. Methods 81 patients with migraines were enrolled in this study. The patients received SGB with 6 ml of 0.15% ropivacaine once every week for four times. Migraine was assessed with the Migraine Disability Assessment Scale (MIDAS) at baseline and three-months follow-up (Tm). The numerical rating scale (NRS) score at baseline, one day after treatment (Td) and Tm, the frequency of analgesic use in 3 months and the side effects were also recorded at the same time. Results The NRS score of migraine subjects decreased significantly from 7.0 (2.0) to 3.0 (1.0) at Td and 2.0 (2.0) at Tm (vs baseline, P < 0.01). The MIDAS total scores were 14.0 (10.5) at baseline and 7.0 (4.5) at Tm (P < 0.001). During the three months, the frequency of analgesic consumption was decreased from 6.2 ± 2.8 to 1.9 ± 1.8. There were no serious side effects. Conclusions This study confirmed that ultrasound-guided SGB is an effective method to treat migraines. This technique can reduce pain and disability and then improve the quality of life of patients with migraines.

Neuropathic pain, caused by a lesion or dysfunction of the somatosensory nervous system, is a severe debilitating condition with which clinical treatment remains challenging. Jun activation domain-binding protein (JAB1) is a multifunctional protein that participates in several signaling pathways, controlling cell proliferation and apoptosis. However, the expression and possible function of JAB1 in the pathogenesis of neuropathic pain has not been elucidated. This study aimed to investigate the possible involvement of JAB1. Here, employing a neuropathic pain model induced by chronic constriction injury (CCI) on rats, we reported the role of JAB1 in the maintenance of neuropathic pain. By western blot, we found that CCI markedly up-regulated JAB1 expression in the dorsal root ganglion (DRG) and spinal cord. Immunofluorescent assay demonstrated that JAB1 was extensively localized in IB4-, CGRP- and NF200-positive neurons in the injured L5 DRG, and mainly co-localized with NeuN in spinal cord. In addition, we showed that CCI induced phosphorylation of p65 and JNK in vivo. Intrathecal injection of JAB1 siRNA significantly attenuated the CCI-induced JNK and p65 phosphorylation and alleviated both mechanical allodynia and heat hyperalgesia in rats. Taken together, these results suggested that JAB1 promotes neuropathic pain via positively regulating JNK and NF-κB activation.