86-23, revised in 1985)

86-23, revised in 1985). Neuropathic surgery (CCD) Under anesthesia by an intraperitoneal injection mixture of ketamine (90 mg/kg) and xylazine (9 mg/kg), the transverse process and intervertebral foramina of L4 and L5 were exposed unilaterally as previously described [12]. from day 3 to day 14 after CCD surgery, as is consistent with the manifestation of allodynia. The BD 1047 (10, 30, 100 mg/kg) administered on postoperative days 0~5 dose-dependently suppressed both the induction of allodynia and the elevation of the spinal pERK expression in a manner comparable with that of gabapentin (100 mg/kg). At 7 days post-CCD surgery, BD1047 (10, 30, 100 mg/kg) administration also produced anti-nociceptive effects on the mechanical and cold allodynia similar with those of gabapentin (100 mg/kg). Therefore, this data suggested that Sig-1R may play an important role in both the development and maintenance of CCD-induced neuropathy. strong class=”kwd-title” Keywords: Allodynia, Dorsal root ganglion, Extracellular signal-regulated kinase, Neuropathic pain, Sigma-1 receptor INTRODUCTION The accumulated data has revealed that sigma-1 receptors (Sig-1R) are a modulator of a variety of receptors and ion channels, and they act as amplifiers in signal transduction cascades [1]. It has been shown in Sig-1R knockout mice that Pixantrone both phases of formalin-induced paw licking/biting Pixantrone behavior are reduced by approximately 55% as compared to that of wild-type animals [2]. We observe that the Sig-1R antagonist BD1047 has an anti-nociceptive effect in several pain models, including formalin-induced pain behaviors and capsaicin-induced headache [3-5]. Moreover, studies with selective Sig-1R ligands and Sig-1R knockout mice have suggested that Sig-1R is essential Rabbit polyclonal to NF-kappaB p65.NFKB1 (MIM 164011) or NFKB2 (MIM 164012) is bound to REL (MIM 164910), RELA, or RELB (MIM 604758) to form the NFKB complex.The p50 (NFKB1)/p65 (RELA) heterodimer is the most abundant form of NFKB. for capsaicin-induced mechanical hypersensitivity [6]. Taken together, the accumulated data from these pain models provides evidence to consider using selective Sig-1R antagonists as an innovative approach for treating nociceptive pain. Peripheral neuropathic pain, which results from damage or dysfunction of peripheral nerves, is one of the most challenging chronic pain conditions to treat as compared with treating nociceptive pain. Major intractable pain symptoms caused by neuropathic pain are known as allodynia evoked by thermal or mechanical stimuli. Our recent study reveals that dehydroepiandrosterone (DHEA) sulphate Pixantrone a proposed endogenous Sig-1R ligand, dose-dependently produces mechanical allodynia in na?ve animals with reversible manner by BD1047 [5]. Moreover, DHEA faciliates the induction of mechanical allodynia in the sciatic nerve injury induced neuropathic pain model in rats, which is blocked BD1047 [6]. These overall study shows that the activation of Sig-1R may evoke mechanical allodynia, thus its selective blockage has a therapeutical potential for neuropathic pain. Supporting to this assumption, cold and mechanical allodynia did not develop in Sig-1R null mice exposed to partial sciatic nerve injury [7]. In addition, a recent study from our laboratories reported that BD1047 administered intrathecally during the induction phase, but not the maintenance phase, significantly attenuated mechanical allodynia following chronic constriction injury of the right sciatic nerve in rats [8]. All this data indicates that spinal activation of Sig-1R is also involved in the sciatic nerve injury-induced pain sensation. On the other hand, activation and sensitization of nociceptive dorsal root ganglion (DRG) neurons can lead to chronic low back pain, sciatica, allodynia and other manifestations of lumbar radiculopathy. This may occur in humans when chronic compression on the DRG (CCD) is evoked by a herniated lumbar disk, or when the DGR is exposed to the herniated nucleus pulposus, but there is minimal morphological abnormality. Pixantrone It is notable that CCD produces profound effects on tetrodotoxin-resistant and tetrodotoxin-sensitive sodium currents, and these effects are different from those caused by sciatic nerve injury [9]. Because the pathological impact of each type of injury is different (soma vs axon), animal models generate distinct or controversial results that need to be specifically analyzed within the context of each experimental condition. Thus, the present study aimed to investigate whether Sig-1R was involved in the CCD induced neuronal excitability during both the induction and maintenance phases. A large number of studies have provided.