Protein kinase C gamma-mediated phosphorylation of GluA1 in the postsynaptic density of spinal dorsal horn neurons accompanies neuropathic pain, and dephosphorylation by calcineurin is associated with prolonged analgesia.

Loss of calcineurin (protein phosphatase 3) activity and protein content in the postsynaptic density (PSD) of spinal dorsal horn neurons was associated with pain behavior after chronic constriction injury (CCI) of the rat sciatic nerve, and intrathecal administration of the phosphatase provided prolonged analgesia (Miletic et al. 2013). In this study, we examined whether one consequence of the loss of calcineurin was the persistent phosphorylation of the GluA1 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropioinic acid (AMPAR) receptors in the PSD.

Loss of calcineurin in the spinal dorsal horn contributes to neuropathic pain, and intrathecal administration of the phosphatase provides prolonged analgesia.

Calcineurin (protein phosphatase 3) regulates synaptic plasticity in the brain. The development of neuropathic pain appears dependent on some of the same mechanisms that underlie brain synaptic plasticity. In this study, we examined whether calcineurin regulates chronic constriction injury (CCI)-elicited plasticity in the spinal dorsal horn.

Loose ligation of the rat sciatic nerve elicits early accumulation of Shank1 protein in the post-synaptic density of spinal dorsal horn neurons.

Plasticity in the spinal dorsal horn may contribute to the development of pain following peripheral nerve injury. Shank proteins are a constituent family of the post-synaptic density (PSD), and they may play a role in synaptic plasticity through activity-dependent synaptic remodeling and growth. In this study we examined the early consequences of the loose ligation of the sciatic nerve on Shank1 protein and message levels in the PSD of spinal dorsal horn neurons.

Early changes in Homer1 proteins in the spinal dorsal horn are associated with loose ligation of the rat sciatic nerve.

Background: Plasticity in the spinal dorsal horn is thought to underlie, at least in part, pain behavior after peripheral nerve injury. Homer1 proteins play an important role in synaptic plasticity through an activity-dependent remodeling of the postsynaptic density (PSD). In this study, we examined the early consequences of the loose ligation of the sciatic nerve on the levels of Homer1a and Homer1b/c proteins in the PSD of spinal dorsal horn neurons.

Functional adaptation to loading of a single bone is neuronally regulated and involves multiple bones.

Regulation of load-induced bone formation is considered a local phenomenon controlled by osteocytes, although it has also been hypothesized that functional adaptation may be neuronally regulated. The aim of this study was to examine bone formation in multiple bones, in response to loading of a single bone, and to determine whether adaptation may be neuronally regulated. Load-induced responses in the left and right ulnas and humeri were determined after loading of the right ulna in male Sprague-Dawley rats (69 +/- 16 days of age).

Midazolam administration reverses thermal hyperalgesia and prevents gamma-aminobutyric acid transporter loss in a rodent model of neuropathic pain.

Background: Loss of gamma-aminobutyric acid (GABA) inhibition in the spinal dorsal horn may contribute to neuropathic pain. Here we examined whether systemic administration of the benzodiazepine midazolam would alleviate thermal hyperalgesia due to chronic constriction injury (CCI) of the sciatic nerve.

Methods: Hyperalgesia was evaluated with the thermal paw withdrawal latency test before, and 3 and 7 days after CCI.

Loose ligation of the sciatic nerve is associated with TrkB receptor-dependent decreases in KCC2 protein levels in the ipsilateral spinal dorsal horn.

Significant decreases in the protein levels of potassium-chloride co-transporter 2 (KCC2) were detected in the ipsilateral spinal dorsal horn 4h following loose ligation of the sciatic nerve. These decreases were associated with a change in hindlimb weight distribution suggestive of pain behavior. In contrast, no changes in GABA-A receptor subunit alpha-1 levels were detected.

Analgesic efficacy and respiratory effects of butorphanol and morphine in turtles.

Objective: To test the hypothesis that butorphanol or morphine induces antinociception with minimal respiratory depression in conscious red-eared slider turtles.

Design: Prospective crossover study.

Animals: 37 adult male and female red-eared slider turtles (Trachemys scripta).

B1 and TRPV-1 receptor genes and their relationship to hyperalgesia following spinal cord injury.

Study Design: Laboratory investigation of pain behavior following spinal cord injury.

Objective: To explore changes in the spinal cord expression of nociceptive genes following spinal cord injury (SCI) as they relate to the manifestation of pain behavior in rats.

Summary Of Background Data: Neuropathic pain following SCI is common, disabling, and largely untreatable.

Loose ligation of the sciatic nerve in rats elicits transient up-regulation of Homer1a gene expression in the spinal dorsal horn.

Changes in the expression of many genes underlie injury-elicited plasticity in the spinal dorsal horn. Homer1 is a recently identified gene that appears to play a critical role in the expression of synaptic plasticity in several brain regions, including the hippocampus. In this study we investigated the early consequences of chronic constriction injury of the sciatic nerve on Homer1 gene expression in the spinal dorsal horn.

Increased levels of Homer1b/c and Shank1a in the post-synaptic density of spinal dorsal horn neurons are associated with neuropathic pain in rats.

Activity-dependent plasticity in the spinal dorsal horn may underlie the development of neuropathic pain following peripheral nerve injury. In this study we examined whether the expression and loss of behavioral signs of neuropathic pain were associated with changes in the content of the scaffolding proteins Homer and Shank in the post-synaptic density (PSD) of the spinal dorsal horn. In animals exhibiting thermal hyperalgesia and differential weight-bearing behavior 7 days after loose ligation of the sciatic nerve the levels of Homer1b/c and Shank1a were significantly greater than in control, uninjured or sham-operated animals.

Multiple kinase pathways mediate the early sciatic ligation-associated activation of CREB in the rat spinal dorsal horn.

Phosphorylation of the cyclic AMP response element-binding protein (CREB) in the spinal dorsal horn may critically contribute to chronic pain following peripheral nerve injury. We employed inhibitors and activators of protein kinase A (PKA), protein kinase C (PKC), extracellular signal-regulated kinase 1 and 2 (ERK1/2) and calcium/calmodulin-dependent kinase II (CaMKII) to examine whether these kinases individually or in concert mediate the increase in CREB phosphorylation that is evident as early as 2 h after loose ligation of the sciatic nerve. Specific inhibitors of each kinase significantly attenuated the ligation-associated CREB phosphorylation when compared to saline-treated animals.

Brain-derived neurotrophic factor-elicited or sciatic ligation-associated phosphorylation of cyclic AMP response element binding protein in the rat spinal dorsal horn is reduced by block of tyrosine kinase receptors.

Brain-derived neurotrophic factor (BDNF) and cyclic AMP response element binding protein (CREB) may critically contribute to injury-associated plasticity and thus to the development of persistent pain. In the present study we examined the potential interaction between CREB and BDNF in the spinal dorsal horn. Significant CREB phosphorylation was elicited by local application of BDNF (1 microg) onto the spinal dorsal horn of control, uninjured animals.

Protein kinase A contributes to sciatic ligation-associated early activation of cyclic AMP response element binding protein in the rat spinal dorsal horn.

We examined whether early injury-associated activation of cyclic AMP response element binding protein (CREB) in the spinal dorsal horn was mediated by the cyclic AMP-dependent protein kinase A (PKA) pathway. Significant increases in the levels of phosphorylated CREB (pCREB), phosphorylated PKAIIalpha regulatory subunit (pPKA), and PKAalpha catalytic subunit (PKAalpha cat) were elicited 2 h after loose ligation of the sciatic nerve. These injury-elicited increases were significantly reduced by dorsal horn application of the cell-permeable PKA inhibitor Rp-8-Br-cAMPS.

Muscimol prevents long-lasting potentiation of dorsal horn field potentials in rats with chronic constriction injury exhibiting decreased levels of the GABA transporter GAT-1.

The inhibitory activity of gamma-aminobutyric acid (GABA) is considered critical in setting the conditions for synaptic plasticity, and many studies support an important role of GABA in the suppression of nociceptive transmission in the dorsal horn. Consequently, any injury-induced modification of the GABA action has the potential to critically modify spinal synaptic plasticity. We have previously reported that chronic constriction injury of the sciatic nerve was accompanied by long-lasting potentiation of superficial spinal dorsal horn field potentials following high-frequency tetanus.

Increases in the phosphorylation of cyclic AMP response element binding protein (CREB) and decreases in the content of calcineurin accompany thermal hyperalgesia following chronic constriction injury in rats.

Plasticity in the spinal dorsal horn may underlie the development of chronic pain following peripheral nerve injury or inflammation. In this study, we examined whether chronic constriction injury of the sciatic nerve was associated with changes in the immunoreactive content of cyclic AMP response element binding protein (CREB), protein kinase A (PKA), and calcineurin Aalpha and Abeta in the spinal dorsal horn. In animals exhibiting thermal hyperalgesia as a behavioral sign of neuropathic pain 7 days after loose ligation of the sciatic nerve (chronic constriction injury), there was a significant increase in the content of phosphorylated (activated) CREB (pCREB).

Continual systemic infusion of lidocaine provides analgesia in an animal model of neuropathic pain.

We examined whether continual constant-rate infusion of lidocaine would provide analgesia during the initial post-injury phase in the chronic constriction injury model of neuropathic pain. Male Sprague-Dawley rats were divided into control and ligated groups and infused with saline or lidocaine (0.15, 0.

Increases in the concentration of brain derived neurotrophic factor in the lumbar spinal dorsal horn are associated with pain behavior following chronic constriction injury in rats.

Animals exhibiting thermal hyperalgesia as a sign of neuropathic pain 7 days after loose ligation of the sciatic nerve exhibited a significant increase in the concentration of brain derived neurotrophic factor (BDNF) in their lumbar spinal dorsal horn. In contrast, following the disappearance of thermal hyperalgesia 28 days after loose ligation of the sciatic nerve, there were no differences in BDNF levels between control animals and those with sciatic ligations. These data suggest a close association in the timeline of the development and disappearance of behavioral signs of neuropathic pain with changes in BDNF levels in the lumbar spinal dorsal horn, and lend further support to the notion that plasticity in the processing of sensory information in the spinal dorsal horn may contribute to the development of persistent pain.