Intrathecal clonidine for postoperative analgesia in elderly patients: the influence of baricity on hemodynamic and analgesic effects.

Intrathecal (IT) clonidine is an effective analgesic, but it also produces hemodynamic depression and sedation which are likely to be related to IT clonidine's cephalad spread within the cerebrospinal fluid. We hypothesized that IT clonidine's side effects could be reduced without compromising the duration and quality of analgesia by injecting clonidine IT in a hyperbaric solution and elevating the patient's trunk. We prospectively randomized 30 elderly patients to receive IT 150 microg of either isobaric (ISO) or hyperbaric (HYPER) clonidine for postoperative analgesia after surgical repair of traumatic hip fracture.

Spinal adenosine receptor activation reduces hypersensitivity after surgery by a different mechanism than after nerve injury.

Background: Intrathecal adenosine has antinociceptive effects under conditions of hypersensitivity. T62 (2-amino-3-(4-chlorobenzoyl)-5,6,7,8-tetrahydrobenzothiophen) is an allosteric adenosine receptor modulator that enhances adenosine binding to the A1 receptor. Intrathecal T62 reduces hypersensitivity to mechanical stimuli in a rat model of neuropathic pain by a circuit that totally relies on activation of alpha2 adrenoceptors.

Repeated dosing with oral allosteric modulator of adenosine A1 receptor produces tolerance in rats with neuropathic pain.

Background: The positive allosteric adenosine receptor modulator, T62 (2-amino-3-(4-chlorobenzoyl)-5,6,7,8-tetrahydrobenzothiophene), has been shown to reduce mechanical allodynia in a rat model of neuropathic pain. However, whether chronic oral T62 retains efficacy in this pain model has not been examined. Therefore, the authors studied antiallodynic effects of chronic oral T62 in spinal nerved-ligated rats, as well as motor and sedative behavioral effects.

Intrathecal but not intravenous opioids release adenosine from the spinal cord.

Unlabelled: Opioids increase spinal release of adenosine in rats, and analgesia from systemic and intrathecal morphine is reduced in animals by adenosine receptor antagonists. We performed 3 studies to determine whether opioid administration also induces adenosine release in humans. To determine the effect of intrathecal opioid exposure, 15 women received intrathecal fentanyl, 50 microg, or saline, and cerebrospinal fluid was sampled at 2-minute intervals for 6 minutes before surgery.

Cystatin C in cerebrospinal fluid is not a diagnostic test for pain in humans.

A recent subtractive cDNA cloning study in rats demonstrated an unexpected increase in expression of the proteinase inhibitor, cystatin C in the spinal cord during acute peripheral inflammation, suggesting this protein may be involved in the pathogenesis of persistent pain. A subsequent study of 10 women suggested that prolonged labor pain resulted in increased cystatin C concentrations in cerebrospinal fluid, and that this could be used as a biomarker for pain. To confirm and extend these observations, we measured cystatin C concentrations in cerebrospinal fluid in 131 subjects: 30 normal volunteers without pain, 25 women at elective cesarean section without pain, 60 women in labor with severe pain, and 16 patients with chronic neuropathic pain and tactile allodynia.

Intraspinal adenosine induces spinal cord norepinephrine release in spinal nerve-ligated rats but not in normal or sham controls.

Background: Intrathecal adenosine is antinociceptive under conditions of central sensitization, but not in response to acute stimuli in normals. The reasons for this selective circumstance of action remain unclear, but some evidence links adenosine's antinociceptive effects to release of norepinephrine by terminals in the spinal cord. The purpose of this study was to test whether spinal adenosine induces norepinephrine release selectively in settings of hypersensitivity.

Spinal adrenergic and cholinergic receptor interactions activated by clonidine in postincisional pain.

Background: Previous pharmacologic and molecular studies suggest that the alpha(2)-adrenoceptor subtype A is the target for spinally administered alpha(2)-adrenergic agonists, i.e., clonidine, for pain relief.

Age-related morphological impairments in the rat hippocampus following developmental lead exposure: an MRI, LM and EM study.

Lead is one of the most common neurotoxic metals present in our environment. Chronic developmental lead exposure is known to be associated with cognitive dysfunction in children. Functional and morphological impairment of the rat brain has also been reported in the hippocampus (Hi) following developmental lead exposure.

Allosteric adenosine receptor modulation reduces hypersensitivity following peripheral inflammation by a central mechanism.

Activation of adenosine A1 receptors by endogenous adenosine or synthetic agonists produces antinociception in animal models of acute pain and also reduces hypersensitivity in models of inflammatory and nerve-injury pain. Allosteric adenosine modulators facilitate and potentiate the action of adenosine agonists at the A1 receptors. The purpose of the current study was to examine the effect and site of action for an allosteric adenosine modulator, T62 [2-amino-3-(4-chlorobenzoyl)-5,6, 7,8-tetrahydrobenzothiophene], in rat models of acute pain and inflammation.

[Application of SPECT bone scan for multiple myeloma].

Objective: To study the diagnostic value of SPECT for multiple myeloma (MM).

Methods: Single photon emission computed tomography (SPECT) bone scan, marrow puncturing, x-ray and other related examinations were performed in 46 patients with MM. We analysed the diagnostic value of SPECT bone scan combined with marrow puncturing and other examinations for MM.

Peripheral nerve injury alters the alpha2 adrenoceptor subtype activated by clonidine for analgesia.

Background: Previous studies suggest that the alpha adrenoceptor subtype is the target for spinally administered alpha -adrenergic agonists, clonidine, for pain relief. However, ST 91, a preferential alpha adrenoceptor subtype agonist, induces antinociception, and intrathecally administered alpha antisense oligodeoxynucleotide decreases antinociception induced by clonidine in the rat, suggesting non-A sites may be important as well. Therefore, the authors examined the subtype of alpha adrenoceptor activated by clonidine and ST 91 in normal rats and those with nerve injury-induced hypersensitivity.

Spinal norepinephrine release from nitric oxide species is not increased following peripheral nerve injury in rats.

Alpha(2)-Adrenergic agonists increase the synthesis of nitric oxide (NO) in the spinal cord in both in vitro slice perfusion and in vivo microdialysis. In the normal condition, inhibition of NO synthase (NOS) has little effect on antinociception from alpha(2)-adrenergic agonists. However, following peripheral nerve injury, NOS inhibitors completely block the antihypersensitivity effects of alpha(2)-adrenergic agonists.

Nicotinic acetylcholine receptor regulation of spinal norepinephrine release.

Background: Neuronal nicotinic acetylcholine receptor (nAChR) agonists produce antinociception in animals. nAChRs exist almost exclusively on presynaptic terminals in the central nervous system and stimulate neurotransmitter release. This study tested whether nAChR agonists stimulate spinal release of the neurotransmitter norepinephrine either by direct actions on noradrenergic terminals or indirectly by stimulating release of other neurotransmitters to induce norepinephrine release.

Spinal noradrenergic activation mediates allodynia reduction from an allosteric adenosine modulator in a rat model of neuropathic pain.

Activation of adenosine A1 receptors by endogenous adenosine or synthetic agonists produces anti-nociception in animal models of acute pain and also reduces hypersensitivity in models of inflammatory and nerve-injury pain. Allosteric adenosine modulators facilitate adenosine agonist binding to the A1 receptor. The purpose of the current study was to examine the effect, mechanisms of action, and interaction with noradrenergic systems of intrathecal (i.

Intrathecal adenosine following spinal nerve ligation in rat: short residence time in cerebrospinal fluid and no change in A(1) receptor binding.

Background: Intrathecal adenosine produces a remarkably prolonged effect to relieve mechanical hypersensitivity after peripheral nerve injury in animals. The purpose of the current study was to investigate whether this reflected an alteration in kinetics of adenosine in cerebrospinal fluid or in the number of spinal A1 adenosine receptors after nerve injury.

Methods: Male rats were anesthetized, and the left L5 and L6 spinal nerves were ligated.