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Nerve injury often produces long‐lasting spontaneous pain, hyperalgesia and allodynia that are refractory to treatment, being only partially relieved by clinical analgesics, and often insensitive to morphine. With the aim of assessing its therapeutic potential, we examined the effect of antisense oligonucleotide knockdown of spinal metabotropic glutamate receptor 1 (mGluR1) in neuropathic rats.We chronically infused rats intrathecally with either vehicle, or 50 μg day−1antisense or missense oligonucleotides beginning either 3 days prior to or 5 days after nerve injury. Cold, heat and mechanical sensitivity was assessed prior to any treatment and again every few days after nerve injury.Here we show that knockdown of mGluR1significantly reduces cold hyperalgesia, heat hyperalgesia and mechanical allodynia in the ipsilateral (injured) hindpaw of neuropathic rats.Moreover, we show that morphine analgesia is reduced in neuropathic rats, but not in sham‐operated rats, and that knockdown of mGluR1restores the analgesic efficacy of morphine.We also show that neuropathic rats are more sensitive to the excitatory effects of intrathecally injected N‐methyl‐D‐aspartate (NMDA), and have elevated protein kinase C (PKC) activity in the spinal cord dorsal horn, two effects that are reversed by knockdown of mGluR1.These results suggest that activity at mGluR1contributes to neuropathic pain through interactions with spinal NMDA receptors and PKC, and that knockdown of mGluR1may be a useful therapy for neuropathic pain in humans, both to alleviate pain directly, and as an adjunct to opioid analgesic treatment.

THE effect of the adenosine triphosphate (ATP)-sensitive potassium (KATP) channel blocker, glibenclamide, on adenosine-induced postsynaptic hyperpolarization was studied by means of intracellular recording techniques in TTX-treated CA1 neurones in the rat hippocampal slice. Glibenclamide applied in the CSF perfusion fluid at 30 μM reversibly depressed the 2-chloroadenosine-induced hyperpolarization and the increase in the membrane conductance. It is suggested that adenosine induces the opening of potassium channels in the postsynaptic membrane of CA1 neurones, including KATPchannels in the mammalian central nervous system (CNS).

TO examine the specific roles of group I metabotropic glutamate receptors (mGluRs) in nociceptive processing, we examined the effects of intrathecal (i.t.) treatment with antibodies raised against the C-terminals of mGluR1and mGluR5in various rat pain models. The effects of anti-mGluR1IgG and anti-mGluR5IgG were assessed in a model of persistent pain induced by intrathecal administration of the mGluR1/5agonist DHPG, as well as in models of heat pain (plantar test), chemical pain (formalin test) and neuropathic pain. DHPG-induced spontaneous nociceptive behaviours (SNB) were significantly attenuated by i.t. treatment with either anti-mGluR1IgG (30 μg) or anti-mGluR5IgG (10 and 3 0μg). Neither anti-mGluR1IgG (30 μg) nor anti-mGluR5IgG (30 μg) significantly increased response latencies to noxious heat in the plantar test, compared with anti-rat IgG (control IgG). Moreover, neither antibody (3 0μg) significantly reduced formalin pain scores as compared to control IgG. However, i.t. treatment with anti-mGluR1IgG (30 μg) or anti-mGluR5IgG (30 μg) significantly reduced cold hyper-sensitivity exhibited 8 days after constriction injury of the sciatic nerve, supporting the contention that group I mGluRs play a role in the development of neuropathic pain. Because these antibodies were effective against neuropathic pain, and not acute heat or chemical noxious stimuli, these results suggest that mGluRs are involved in nociceptive processing in chronic pain states rather than signaling acute noxious stimuli, and that DHPG-induced pain may be mediated by similar mechanisms as neuropathic pain.

Physiological experiments were run to examine the effects of noxious thermal stimulation of one hindpaw on the tail-flick reflex in the lightly anesthetized rat. Male Sprague-Dawley rats were anesthetized with an i.p. injection of a mixture of Na-pentobarbital (20 mg/kg) and chloral hydrate (120 mg/kg). After baseline readings were taken in the tail-flick test, either a non-noxious or a noxious stimulus was applied which consisted of immersion of one hindpaw in water at 40, 45, 50 or 55°C for 1.5 min. After immersion, tail-flick readings were taken at 3-min intervals for at least 16 min. Paw immersion in water at 55°C induced an antinociceptive response, consisting of an increase in the reaction time, at 0.5 min after immersion. Recovery to baseline levels occurred over the next 3–6 min. Immersion at lower temperatures provoked smaller antinociceptive responses, except at 40°C, where readings remained around the baseline values. The increase in reaction time in response to immersion at 55°C was attenuated or blocked by the novel, nonpeptide substance P (NK-1) receptor antagonist, CP-96,345, administered s.c. 30 or 60 min, respectively, prior to paw immersion. Similar injection of CP-96,344, the inactive stereoisomer, had no effect on the response, while another NK-1 receptor antagonist, CP-99,994, also attenuated the antinociceptive effect of the immersion. The increase in reaction time induced by immersion at 55°C was absent in animals treated neonatally with capsaicin. This nociceptive response was blocked by the broad spectrum opiate antagonist, naloxone (10 mg/kg i.p.) given 20 min before paw immersion. The data provide evidence that a noxious stimulus produces an intensity-related heterosegmental antinociceptive effect and that C-fibers, and NK-1 and opiate receptors are involved in mediating this effect.

In this study, a continuous method based on an amperometric principle of determining fluorides in water is presented. The electrochemical cell utilizes a high‐purity aluminum measuring electrode and an aluminum alloy counter‐electrode. The cell's response is virtually instantaneous, permitting the device to act as an ultimate watchdog against fluoride feeder malfunction.

Presents several letters to the editor referencing articles and topics published in previous issues. Views on the decision rendered by an Hungarian court that it is a crime to praise the United States in Hungary; Suggestion for more male teachers in the U.S. schools; Appreciation for the review of John R. White's book.

The article discusses the importance of the military logistics concept of sealift in ensuring the sustainment of operations of the U.S. Army. It outlines details on the concept which requires the use of cargo ships for the deployment of military assets. Topics discussed include the support given to the logistics support system of the U.S. Department of Defense (DoD) by the Military Sealift Command of the U.S. Navy and details on funding requirements for the strategy.