Single intrathecal administration of the transcription factor decoy AYX1 prevents acute and chronic pain after incisional, inflammatory, or neuropathic injury.

The persistence of pain after surgery increases the recovery interval from surgery to a normal quality of life. AYX1 is a DNA-decoy drug candidate designed to prevent post-surgical pain following a single intrathecal injection. Tissue injury causes a transient activation of the transcription factor EGR1 in the dorsal root ganglia-dorsal horn network, which then triggers changes in gene expression that induce neuronal hypersensitivity.

Ketoprofen produces modality-specific inhibition of pain behaviors in rats after plantar incision.

Background: Postoperative pain remains a significant problem despite optimal treatment with current drugs. Nonsteroidal antiinflammatory drugs reduce inflammation and provide analgesia but are associated with adverse side effects.

Methods: We tested low doses (0.

Differential effect of capsaicin treatment on pain-related behaviors after plantar incision.

Unlabelled: We evaluated the effect of infiltration of dilute solutions of capsaicin, administered before plantar incision, on 3 pain-related behaviors: guarding pain, heat-withdrawal latency, and mechanical-withdrawal threshold. Perineural application of capsaicin was also studied and the appearance of the wound was also evaluated. Dilute solutions of capsaicin .

Epidural tezampanel, an AMPA/kainate receptor antagonist, produces postoperative analgesia in rats.

Background: We evaluated the epidural administration of tezampanel, a non-N-methyl-d-aspartate receptor antagonist, in a rat model for postoperative pain. We sought to determine if this drug affects nociception when administered epidurally by testing its effects on responses to heat in normal rats. The effects of epidural tezampanel on pain-related behaviors in rats that underwent plantar incision were also studied.

Increased nerve growth factor after rat plantar incision contributes to guarding behavior and heat hyperalgesia.

Acutely, nerve growth factor (NGF) exerts profound effects on nociceptive transmission and produces pain and hyperalgesia. In the present study, we sought to determine the tissue levels and role of NGF after a plantar incision. A substantial increase in NGF protein expression occurred in skin 4-h, 1-day and 2-days and 5-days after incision comparing contralateral uninjured skin.

Changes in tissue pH and temperature after incision indicate acidosis may contribute to postoperative pain.

Background: Incisional pain is a common form of acute pain. Previously, the authors studied persistent pain behaviors caused by incisions, using animal models for postoperative pain. In this study, the authors measured tissue pH and hind paw temperature before and after incision to understand factors that may activate and sensitize nociceptors in the incision.

Effect of blockade of nerve growth factor and tumor necrosis factor on pain behaviors after plantar incision.

Unlabelled: To examine the role of nerve growth factor (NGF) in postoperative pain, we administered the tyrosine kinase A (Trk A) immunoglobulin G (IgG) fusion (1 to 10 mg/kg) molecule before and after plantar incision. We also pretreated rats with a tumor necrosis factor receptor (TNFr) protein, p75 IgG fusion protein (5 to 10 mg/kg), to study the role of endogenous TNF in the development of pain behaviors after incision. Rats underwent a plantar incision, and responses to punctate and nonpunctate mechanical stimuli and withdrawal latency to radiant heat were measured.

A-317491, a novel potent and selective non-nucleotide antagonist of P2X3 and P2X2/3 receptors, reduces chronic inflammatory and neuropathic pain in the rat.

P2X3 and P2X2/3 receptors are highly localized on peripheral and central processes of sensory afferent nerves, and activation of these channels contributes to the pronociceptive effects of ATP. A-317491 is a novel non-nucleotide antagonist of P2X3 and P2X2/3 receptor activation. A-317491 potently blocked recombinant human and rat P2X3 and P2X2/3 receptor-mediated calcium flux (Ki = 22-92 nM) and was highly selective (IC50 >10 microM) over other P2 receptors and other neurotransmitter receptors, ion channels, and enzymes.

Effect of intrathecal non-NMDA EAA receptor antagonist LY293558 in rats: a new class of drugs for spinal anesthesia.

Background: Excitatory amino acid receptors are important for both sensory and motor function in the spinal cord. We studied the effects of intrathecal LY293558, a competitive non-N-methyl-D-aspartate excitatory amino acid receptor antagonist, on motor and sensory function in rats to determine whether drugs blocking these receptors could potentially be used as alternative agents to local anesthetics for spinal anesthesia.

Methods: Rats were tested before and 15-240 min after intrathecal injection of 5 nmol (in 10 microl) LY293558.