Dehydroandrographolide succinate attenuates dexamethasone-induced skeletal muscle atrophy by regulating Akt/GSK3β and MuRF-1 pathways.

Andrographis paniculata (AGPA) is known for its wide-ranging biological activities, including antiviral, antipyretic, and anticancer properties. However, its effects on muscle atrophy have not been well understood. This study investigates the impact of andrographolide (AD) and dehydroandrographolide succinate (DAS), key components of AGPA, on skeletal muscle atrophy using in vitro and in vivo models.

Acidic pH facilitates peripheral αβmeATP-mediated nociception in rats: differential roles of P2X, P2Y, ASIC and TRPV1 receptors in ATP-induced mechanical allodynia and thermal hyperalgesia.

Peripheral ischemia is commonly associated with an increase in tissue ATP concentration and a decrease in tissue pH. Although in vitro data suggest that low tissue pH can affect ATP-binding affinities to P2 receptors, the mechanistic relationship between ATP and low pH on peripheral nociception has not been fully examined. This study was designed to investigate the potential role of an acidified environment on intraplantar αβmeATP-induced peripheral pain responses in rats.

An increase in spinal dehydroepiandrosterone sulfate (DHEAS) enhances NMDA-induced pain via phosphorylation of the NR1 subunit in mice: involvement of the sigma-1 receptor.

Our laboratory has recently demonstrated that an increase in the spinal neurosteroid, dehydroepiandrosterone sulfate (DHEAS) facilitates nociception via the activation of sigma-1 receptors and/or the allosteric inhibition GABA(A) receptors. Several lines of evidence have suggested that DHEAS positively modulates N-methyl-d-aspartate (NMDA) receptor activity within the central nervous system. Moreover, we have demonstrated that the activation of sigma-1 receptors increases NMDA receptor activity.

Sigma-1 receptor-induced increase in murine spinal NR1 phosphorylation is mediated by the PKCalpha and epsilon, but not the PKCzeta, isoforms.

Our previous studies have demonstrated that intrathecal (i.t.) administration of a sigma-1 receptor agonist facilitated peripheral nociception via calcium-dependent second messenger cascades including protein kinase C (PKC).

Peripheral acid-sensing ion channels and P2X receptors contribute to mechanical allodynia in a rodent thrombus-induced ischemic pain model.

Unlabelled: We have previously established a thrombus-induced ischemic pain (TIIP) model in the rat, which mimics the pathophysiology of ischemic pain in patients with peripheral arterial disease. Because ischemia commonly induces acidosis and ATP release, one of the goals of this study was to investigate the role of acid-sensing ion channels (ASICs), transient receptor potential vanilloid-1 (TRPV1) receptors, and P2X receptors in the maintenance of ischemia-induced mechanical allodynia (MA). To test this, amiloride (an ASIC blocker), AMG-9810 (a TRPV1 blocker), or PPADS (a P2Xs antagonist) was intraplantarly injected at day 3 after FeCl(2) application onto the femoral artery.

Intrathecal injection of carbenoxolone, a gap junction decoupler, attenuates the induction of below-level neuropathic pain after spinal cord injury in rats.

The most common type of chronic pain following spinal cord injury (SCI) is central neuropathic pain and SCI patients typically experience mechanical allodynia and thermal hyperalgesia. The present study was designed to examine the potential role of astrocyte gap junction connectivity in the induction and maintenance of "below-level" neuropathic pain in SCI rats. We examined the effect of intrathecal treatment with carbenoxolone (CARB), a gap junction decoupler, on SCI-induced bilateral thermal hyperalgesia and mechanical allodynia during the induction phase (postoperative days 0 to 5) and the maintenance phase (days 15 to 20) following T13 spinal cord hemisection.

Activation of spinal alpha-2 adrenoceptors, but not mu-opioid receptors, reduces the intrathecal N-methyl-D-aspartate-induced increase in spinal NR1 subunit phosphorylation and nociceptive behaviors in the rat.

Background: A previous study from our laboratories showed that a significant reduction in spinal N-methyl-D-aspartate (NMDA) receptor NR1 subunit phosphorylation (pNR1) is associated with the antiallodynic effect produced by intrathecal (IT) injection of the alpha-2 adrenoceptor agonist, clonidine, in neuropathic rats. In this study, we determined whether the spontaneous pain and increased pNR1 expression induced by NMDA injection are reduced by IT injection of either clonidine or the mu-opioid receptor agonist, [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO).

Methods: We examined the effect of clonidine (20 microg/rat) or DAMGO (1 microg/rat) injection on IT NMDA-induced spontaneous nociceptive behavior and pNR1 expression in the spinal dorsal horn.

Intrathecal injection of the neurosteroid, DHEAS, produces mechanical allodynia in mice: involvement of spinal sigma-1 and GABA receptors.

Background And Purpose: The neurosteroid, dehydroepiandrosterone sulphate (DHEAS) and its non-sulphated form, DHEA, are considered as crucial endogenous modulators of a number of important physiological events. Evidence suggests that DHEAS and DHEA modulate central nervous system-related functions by activating sigma-1 receptors and/or allosterically inhibiting gamma-aminobutyric acid receptor type A (GABA(A)) receptors. As both the sigma-1 receptor and the GABA(A) receptor play important roles in spinal pain transmission, the present study was designed to examine whether intrathecally injected DHEAS or DHEA affect nociceptive signalling at the spinal cord level.

Acupoint stimulation with diluted bee venom (apipuncture) potentiates the analgesic effect of intrathecal clonidine in the rodent formalin test and in a neuropathic pain model.

Unlabelled: Although intrathecal (i.t.) administration of the alpha(2)-adrenoceptor agonist clonidine has a pronounced analgesic effect, the clinical use of clonidine is limited by its side effects.

Intrathecal injection of the sigma(1) receptor antagonist BD1047 blocks both mechanical allodynia and increases in spinal NR1 expression during the induction phase of rodent neuropathic pain.

Background: Selective blockade of spinal sigma(1) receptors (Sig-1R) suppresses nociceptive behaviors in the mouse formalin test. The current study was designed to verify whether intrathecal Sig-1R antagonists can also suppress chronic neuropathic pain.

Methods: Neuropathic pain was produced by chronic constriction injury (CCI) of the right sciatic nerve in rats.

The anti-arthritic effect of ursolic acid on zymosan-induced acute inflammation and adjuvant-induced chronic arthritis models.

Ursolic acid (UA) is pentacyclic triterpenoic acid that naturally occurs in many medicinal herbs and plants. In this study, we examined the possible suppressive effect of UA extracted from Oldenlandia diffusa on zymosan-induced acute inflammation in mice and complete Freund's adjuvant (CFA)-induced arthritis in rats. UA treatment (per oral) dose-dependently (25-200 mg kg(-1)) suppressed zymosan-induced leucocyte migration and prostaglandin E2 (PGE(2)) production in the air pouch exudates.

A new rat model for thrombus-induced ischemic pain (TIIP); development of bilateral mechanical allodynia.

Patients with peripheral arterial disease (PAD) commonly suffer from ischemic pain associated with severe thrombosis. However, the pathophysiology of peripheral ischemic pain is not fully understood due to the lack of an adequate animal model. In this study, we developed a new rodent model of thrombus-induced ischemic pain (TIIP) to investigate the neuronal mechanisms underlying ischemic pain.

Intrathecal administration of sigma-1 receptor agonists facilitates nociception: involvement of a protein kinase C-dependent pathway.

Sigma sites, originally proposed as opioid receptor subtypes, are currently thought to represent unique receptors with a specific pattern of drug selectivity, a well-established anatomical distribution and broad range of functional roles including potential involvement in nociceptive mechanisms. We have recently demonstrated that intrathecal (i.t.

Intrathecal clonidine suppresses phosphorylation of the N-methyl-D-aspartate receptor NR1 subunit in spinal dorsal horn neurons of rats with neuropathic pain.

Background: Intrathecal (IT) administration of the alpha-2 adrenoceptor agonist, clonidine, produces significant analgesic effects. Although several mechanisms underlying clonidine-induced analgesia have been proposed, the possible interaction with N-methyl-D-aspartate (NMDA) receptors as a major antinociceptive mechanism has not been addressed. We designed the present study to determine whether clonidine or other analgesics can affect spinal NMDA receptor activation in rats with chronic constriction injury (CCI)-induced neuropathy.

Bee venom injection produces a peripheral anti-inflammatory effect by activation of a nitric oxide-dependent spinocoeruleus pathway.

Our recent data, obtained using a zymosan-induced inflammatory air pouch model in mice, have demonstrated that subcutaneous bee venom (BV) injection into the hind limb selectively activates the contralateral brain stem locus coeruleus (LC) and then via a descending noradrenergic pathway and subsequent adrenal medullary catecholamine release induces a potent anti-inflammatory effect. While the efferent limb of this BV-induced neuroimmune anti-inflammatory pathway is well documented, the afferent limb of this pathway is poorly understood. In particular the spinal mechanisms involved with BV activation of the LC are currently unknown.

Depletion of capsaicin-sensitive afferents prevents lamina-dependent increases in spinal N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation associated with thermal hyperalgesia in neuropathic rats.

Phosphorylation of the N-methyl-D-aspartate (NMDA) receptor NR1 subunit (pNR1) in the spinal cord is associated with increased neuronal responsiveness, which underlies the process of central sensitization. Because of the importance of NR1 in central sensitization, the first goal of this study was to examine both time- and lamina-dependent changes in spinal NR1 and pNR1 expression in a chronic constriction injury (CCI) model of neuropathic pain. Increased excitability of capsaicin sensitive primary afferents (CSPAs), which express TRPV1 receptors, also contributes to central sensitization.

A spinal muscarinic M2 receptor-GABAergic disinhibition pathway that modulates peripheral inflammation in mice.

Previous data from our laboratories using the mouse air pouch model demonstrated that intrathecal injection of the cholinomimetic drug, neostigmine, produces a significant peripheral anti-inflammatory effect through activation of spinal muscarinic type 2 receptors. This anti-inflammatory effect is mediated by activation of sympathetic preganglionic neurons and subsequent release of adrenomedullary catecholamines. It has been established that adrenomedullary catecholamine release is controlled by sympathetic preganglionic neurons and that these neurons are modulated by GABAergic inhibitory input.

Peripheral bee venom's anti-inflammatory effect involves activation of the coeruleospinal pathway and sympathetic preganglionic neurons.

There are several reports indicating that the locus coeruleus (LC) is capable of altering immune responses. Moreover, it is well established that the LC is the major source of descending noradrenergic system. Recently we have demonstrated that subcutaneous bee venom (BV) injection dramatically suppressed peripheral inflammation through activation of sympathetic preganglionic neurons (SPNs) leading to release of adreno-medullary catecholamines.