Evaluation of intramuscular ketoprofen and butorphanol as analgesics in chain dogfish (Scyliorhinus retifer)

The mediation of nociception with analgesic medications has not been well documented in elasmobranchs. The purpose of this study was to determine effective analgesic doses of the opioid agonist‐antagonist, butorphanol, and the non‐steroidal anti‐inflammatory drug, ketoprofen, in an elasmobranch. This was evaluated by repetitively assessing minimum anesthetic concentrations of the immersion anesthetic, tricaine methanesulfonate (MS‐222), required to prevent response to noxious stimuli in chain dogfish (Scyliorhinus retifer) when administered multiple doses of each of the analgesics (0.25, 0.5, 1.0, 2.5, and 5.0 mg/kg butorphanol and 1.0, 1.5, 2.0, and 4.0 mg/kg ketoprofen). Baseline concentrations of MS‐222 required to prevent a response to a noxious stimulus were determined for each animal and served as the controls. Although individual animals displayed a reduction in MS‐222 concentration with various doses of both analgesics, no statistically significant difference was noted between control animals and animals given analgesics. It is plausible that unique elasmobranch anatomy, lack of appropriate medication dose or timing of administration, and other physiological factors not yet identified may have contributed to the lack of apparent efficacy of the analgesics evaluated in this study. Zoo Biol 0:1–10, 2006. © 2006 Wiley‐Liss, Inc.     

The clinical significance and function of miR-146 in the promotion of epidural fibrosis

Epidural fibrosis is the main cause of failed back surgery syndrome. To investigate the role of miR-146 in the diagnosis and development of epidural fibrosis. Lumbar disc tissues were collected from 72 lumbar disc herniation patients (45 developed epidural fibrosis and 27 did not). The expression of miR-146 in collected tissues and isolated epidural fibroblasts was detected by RT-qPCR. The relative levels of pro-inflammatory cytokines were analyzed by ELISA. The effect of miR-146 on the proliferation of fibroblasts was evaluated by MTT assay. miR-146 was significantly upregulated in epidural fibrosis patients compared with control patients. The expression of miR-146 was closely associated with the location, lower limb symptom and duration of disease of epidural fibrosis patients, and was positively correlated with the relative levels of pro-inflammatory cytokines. Moreover, miR-146 could discriminate epidural fibrosis patients from control patients. In isolated epidural fibroblasts, the overexpression of miR-146 dramatically enhanced its proliferation and the inflammatory response. miR-146 serves as a diagnostic biomarker for the early detection of epidural fibrosis. The upregulation of miR-146 enhanced the fibroblasts proliferation and inflammatory response in epidural fibrosis. This study provides a novel potential therapeutic target for epidural fibrosis.     

Synergistic analgesic effects between neuronostatin and morphine at the supraspinal level

Neuronostatin, a 13-amino acid peptide, is encoded in the somatostatin pro-hormone. I.c.v. administration of neuronostatin produces a significant antinociceptive effect in the mouse tail-flick test, which is mediated by endogenous opioid receptor. However, the direct functional interaction between morphine and neuronostatin has not been characterized. In the present study, effect of neuronostatin on morphine analgesia was investigated in the tail-flick test. Our findings showed that i.c.v. administration of neuronostatin (0.3 nmol/mouse i.c.v.) significantly enhanced the antinociceptive effect of morphine (2.5, 5 or 10 μg/kg) at the supraspinal level. Results of antagonism experiments suggested that the synergistic analgesia induced by morphine and neuronostatin was mediated by μ- and к-opioid receptors not δ-opioid receptor. In conclusion, there may be a cascade amplification phenomenon when morphine and neuronostatin were co-administered in acute pain model. The above results provide evidence for the potential use of neuronostatin in combination with morphine to control pain and addiction.     

Inhibitory Kcnip2 neurons of the spinal dorsal horn control behavioral sensitivity to environmental cold

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Insights into peptide and protein function: a convergent approach.

From viruses to multicellular organisms, life is inseparable from the genetic instructions aimed at regulating its maintenance, division, multiplication, differentiation and death (apoptosis). Over the past 15 years, structural studies have begun to resolve the complex reactions involved in these fundamental processes in biology. The three-dimensional representations of the complexes formed with peptides and/or proteins have allowed interpretation of the biochemical data and formulation of novel hypotheses about the control and execution of these processes. Moreover, they have opened the way to rational approaches for designing compounds able to interfere with these crucial events in normal or pathological conditions. Various results obtained in our laboratory in these fields are briefly summarized in this review.     

Long-term potentiation in the anterior cingulate cortex and chronic pain

Glutamate is the primary excitatory transmitter of sensory transmission and perception in the central nervous system. Painful or noxious stimuli from the periphery ‘teach’ humans and animals to avoid potentially dangerous objects or environments, whereas tissue injury itself causes unnecessary chronic pain that can even last for long periods of time. Conventional pain medicines often fail to control chronic pain. Recent neurobiological studies suggest that synaptic plasticity taking place in sensory pathways, from spinal dorsal horn to cortical areas, contributes to chronic pain. Injuries trigger long-term potentiation of synaptic transmission in the spinal cord dorsal horn and anterior cingulate cortex, and such persistent potentiation does not require continuous neuronal activity from the periphery. At the synaptic level, potentiation of excitatory transmission caused by injuries may be mediated by the enhancement of glutamate release from presynaptic terminals and potentiated postsynaptic responses of AMPA receptors. Preventing, ‘erasing’ or reducing such potentiation may serve as a new mechanism to inhibit chronic pain in patients in the future.     

Stable fly, Stomoxys calcitrans, mouthpart removal influences stress and anticipatory responses in mice

Abstract Biting fly attack induces a variety of stress and anxiety related changes in the physiology and behaviour of the target animals. Significant reductions in pain, or more appropriately, nociceptive sensitivity (latency of a foot-lifting response to an aversive thermal stimulus), are evident in laboratory mice after a 1 h exposure to stable flies, Stomoxys calcitrans. The role of the various components of biting fly attack in the development of this stress-induced reduction in pain sensitivity (analgesia) is, however, unclear. This study demonstrates that fly-naive mice do not exhibit a stress-induced analgesia when exposed to stable flies whose biting mouthparts have been removed. In contrast, mice that have been previously exposed to intact stable flies exhibit significant analgesia when exposed to flies that are incapable of biting. However, the level of analgesia induced is lower than that elicited by exposure to intact stable flies. Exposure to non-biting house flies, Musca domestica , has no effect on nociceptive sensitivity. It appears that the actual bite of the stable fly is necessary for the induction of analgesia and probably other stress and anxiety associated responses in fly naive mice. However, mice rapidly learn to recognize biting flies and exhibit significant, possibly anticipatory analgesic responses to the mere presence of biting flies.