Modulation of Spinal Nociceptive Transmission by Sub-Sensory Threshold Spinal Cord Stimulation in Rats After Nerve Injury.

Objectives: High-frequency spinal cord stimulation (SCS) administered below the sensory threshold (subparesthetic) can inhibit pain, but the mechanisms remain obscure. We examined how different SCS paradigms applied at intensities below the threshold of Aβ-fiber activation (sub-sensory threshold) affect spinal nociceptive transmission in rats after an L5 spinal nerve ligation (SNL).

Materials And Methods: Electrophysiology was used to record local field potential (LFP) at L4 spinal cord before, during, and 0-60 min after SCS in SNL rats.

The Impact of Electrical Charge Delivery on Inhibition of Mechanical Hypersensitivity in Nerve-Injured Rats by Sub-Sensory Threshold Spinal Cord Stimulation.

Objectives: Spinal cord stimulation (SCS) represents an important neurostimulation therapy for pain. A new ultra-high frequency (10,000 Hz) SCS paradigm has shown improved pain relief without eliciting paresthesia. We aim to determine whether sub-sensory threshold SCS of lower frequencies also can inhibit mechanical hypersensitivity in nerve-injured rats and examine how electric charge delivery of stimulation may affect pain inhibition by different patterns of subthreshold SCS.

Activation of cannabinoid CB1 receptor contributes to suppression of spinal nociceptive transmission and inhibition of mechanical hypersensitivity by Aβ-fiber stimulation.

Activation of Aβ-fibers is an intrinsic feature of spinal cord stimulation (SCS) pain therapy. Cannabinoid receptor type 1 (CB1) is important to neuronal plasticity and pain modulation, but its role in SCS-induced pain inhibition remains unclear. In this study, we showed that CB1 receptors are expressed in both excitatory and inhibitory interneurons in substantia gelatinosa (SG).

T-type calcium channel blocker Z944 restores cortical synchrony and thalamocortical connectivity in a rat model of neuropathic pain.

Oscillations are fundamental to communication between neuronal ensembles. We previously reported that pain in awake rats enhances synchrony in primary somatosensory cortex (S1) and attenuates coherence between S1 and ventral posterolateral (VPL) thalamus. Here, we asked whether similar changes occur in anesthetized rats and whether pain modulates phase-amplitude coupling between VPL and S1.

Effects of Combined Electrical Stimulation of the Dorsal Column and Dorsal Roots on Wide-Dynamic-Range Neuronal Activity in Nerve-Injured Rats.

Objectives: Electrical stimulation at the dorsal column (DC) and dorsal root (DR) may inhibit spinal wide-dynamic-range (WDR) neuronal activity in nerve-injured rats. The objective of this study was to determine if applying electrical conditioning stimulation (CS) at both sites provides additive or synergistic benefits.

Materials And Methods: By conducting in vivo extracellular recordings of WDR neurons in rats that had undergone L5 spinal nerve ligation, we tested whether combining 50 Hz CS at the two sites in either a concurrent (2.

Electrical stimulation of dorsal root entry zone attenuates wide-dynamic-range neuronal activity in rats.

Objectives: Recent clinical studies suggest that neurostimulation at the dorsal root entry zone (DREZ) may alleviate neuropathic pain. However, the mechanisms of action for this therapeutic effect are unclear. Here, we examined whether DREZ stimulation inhibits spinal wide-dynamic-range (WDR) neuronal activity in nerve-injured rats.

Differential effects of subcutaneous electrical stimulation (SQS) and transcutaneous electrical nerve stimulation (TENS) in rodent models of chronic neuropathic or inflammatory pain.

Objectives: Electrical stimulation has been used for many years for the treatment of pain. Present-day research demonstrates that stimulation targets and parameters impact the induction of specific pain-modulating mechanisms. New targets are increasingly being investigated clinically, but the scientific rationale for a particular target is often not well established.

Gene expression profiling and endothelin in acute experimental pancreatitis.

Aim: To analyze gene expression profiles in an experimental pancreatitis and provide functional reversal of hypersensitivity with candidate gene endothelin-1 antagonists.

Methods: Dibutyltin dichloride (DBTC) is a chemical used as a polyvinyl carbonate stabilizer/catalyzer, biocide in agriculture, antifouling agent in paint and fabric. DBTC induces an acute pancreatitis flare through generation of reactive oxygen species.

Descending facilitatory pathways from the rostroventromedial medulla mediate naloxone-precipitated withdrawal in morphine-dependent rats.

Unlabelled: Opioids produce analgesic effects, and extended use can produce physical dependence in both humans and animals. Dependence to opiates can be demonstrated by either termination of drug administration or through precipitation of the withdrawal syndrome by opiate antagonists. Key features of the opiate withdrawal syndrome include hyperalgesia, anxiety, and autonomic signs such as diarrhea.

Attenuation of persistent experimental pancreatitis pain by a bradykinin b2 receptor antagonist.

Objective: The role of bradykinin (BK) receptors in activating and sensitizing peripheral nociceptors is well known. Recently, we showed that spinal dynorphin was pronociceptive through direct or indirect BK receptor activation. Here, we explored the potential role of BK receptors in pain associated with persistent pancreatitis in rats.

Spinal NK-1 receptor-expressing neurons and descending pathways support fentanyl-induced pain hypersensitivity in a rat model of postoperative pain.

The clinically important opioid fentanyl, administered acutely, enhances mechanical hypersensitivity in a model of surgical pain induced by plantar incision. Activity of neurokinin-1 (NK-1) receptor-expressing ascending spinal neurons, descending pathways originating in the rostral ventromedial medulla (RVM), and spinal dynorphin are necessary for the development and maintenance of hyperalgesia during sustained morphine exposure, suggesting that these mechanisms may also be important in opioid enhancement of surgical pain. Therefore, we examined the roles of these mechanisms in sensory hypersensitivity produced by acute fentanyl administration in rats not undergoing surgical incision and in rats undergoing plantar incision.

fMRI of supraspinal areas after morphine and one week pancreatic inflammation in rats.

Abdominal pain is a major reason patients seek medical attention yet relatively little is known about neuronal pathways relaying visceral pain. We have previously characterized pathways transmitting information to the brain about visceral pain. Visceral pain arises from second order neurons in lamina X surrounding the spinal cord central canal.

Reversal of inflammatory and noninflammatory visceral pain by central or peripheral actions of sumatriptan.

Background & Aims: Sumatriptan is used specifically to relieve headache pain. The possible efficacy of sumatriptan was investigated in 2 models of visceral pain.

Methods: Pancreatic inflammation was induced by intravenous injection of dibutyltin dichloride.

Spinal NK-1 receptor expressing neurons mediate opioid-induced hyperalgesia and antinociceptive tolerance via activation of descending pathways.

Opioids can induce hyperalgesia in humans and in animals. Mechanisms of opiate-induced hyperalgesia and possibly of spinal antinociceptive tolerance may be linked to pronociceptive adaptations occurring at multiple levels of the nervous system including activation of descending facilitatory influences from the brainstem, spinal neuroplasticity, and changes in primary afferent fibers. Here, the role of NK-1 receptor expressing cells in the spinal dorsal horn in morphine-induced hyperalgesia and spinal antinociceptive tolerance was assessed by ablating these cells with intrathecal injection of SP-saporin (SP-SAP).

Descending facilitation from the rostral ventromedial medulla maintains visceral pain in rats with experimental pancreatitis.

Background & Aims: Pain is a main complaint of patients with pancreatitis. We hypothesized that such pain is mediated through ascending pathways via the nucleus gracilis (NG) and is dependent on descending facilitatory influences from the rostral ventromedial medulla (RVM).

Methods: A rat model of persistent experimental pancreatitis was used.

Intrathecal gabapentin enhances the analgesic effects of subtherapeutic dose morphine in a rat experimental pancreatitis model.

Background: Morphine sulfate has long been used for analgesia, but clinical applications can be limited by side effects, tolerance, and potential for addiction at therapeutic doses. An agent that produces therapeutic analgesia when coadministered with low-dose morphine could have important clinical uses. The anticonvulsant agent gabapentin has been identified as having antihyperalgesic properties acting on the alpha2delta1 subunit of N-type voltage-activated calcium channels on dorsal root ganglia neurons.

Attenuation of nociception in a model of acute pancreatitis by an NK-1 antagonist.

Substance P (SP) acting at the NK-1 neurokinin receptor has a well-documented role in the transmission and maintenance of nociceptive information. SP is found in the majority of fibers innervating the pancreas, and it is up-regulated after pancreatic inflammation. The aim of this study was to investigate the role of the NK-1 receptors in the maintenance of pancreatic nociception.

Intrathecal coadministration of D-APV and morphine is maximally effective in a rat experimental pancreatitis model.

Background: Many studies have demonstrated that either glutamate -methyl-d-aspartate (NMDA) receptor antagonists or opioid receptor agonists provide antinociception. Spinal coadministration of an NMDA receptor antagonist and morphine has an additive action for control of various pain states in animal models. The current study examined spinal coadministration of low doses of NMDA receptor antagonist, D-(-)-2-Amino-5-phosphonovalerate (D-APV), and mu-opioid receptor agonist, morphine sulfate (MS), in reducing visceral nociception using an acute bradykinin induced pancreatitis model in rats.

Nociception in persistent pancreatitis in rats: effects of morphine and neuropeptide alterations.

Background: Most animal models of pancreatitis are short-lived or very invasive. A noninvasive animal model of pancreatitis developed in highly inbred rats by Merkord with symptoms persisting for 3 weeks was adopted in the current study to test its validity as a model of visceral pain in commercially available rats.

Methods: The persistent pancreatitis model was established by tail vein injection of dibutyltin dichloride.

Rapid changes in expression of glutamate transporters after spinal cord injury.

Glutamate is a major excitatory neurotransmitter in the mammalian CNS. After its release, specific transporter proteins rapidly remove extracellular glutamate from the synaptic cleft. The clearance of excess extracellular glutamate prevents accumulation under normal conditions; however, CNS injury elevates extracellular glutamate concentrations to neurotoxic levels.