S80 Poster Sessions / European Journal of Pain 13 (2009) S55–S285

effects than other single or combined drug uses on attenuating

hyperalgesia and edema in this model. On the other hand, DM and

memantine may have different effects on anti-edema, but once

combined use of themmay affect each other, resulting in less effects

on anti-hyperalgesia and anti-edema in this model. (Supported by

NHRI-EX97–9401NP, Taiwan, ROC)

252

GENISTEIN, A SOY ISOFLAVONE, REVERSES MECHANICAL

ALLODYNIA AND OXIDATIVE AND INFLAMMATORY STRESS IN

A DIABETIC MOUSE MODEL OF NEUROPAHIC PAIN

A.E. Valsecchi*, S. Franchi, P. Sacerdote, A.E. Panerai, M. Colleoni.

Departement of Pharmacology, Chemotherapy and Medical Toxicology

University of Milan, Milan, Italy

Apart from glycaemia control, many drugs have been developed

for the control of diabetes and its complications, but are not

satisfactory in neuropathy control and limited by adverse events.

Genistein, a soy isoflavone, is therapeutic for obesity, diabetes and

cardiovascular diseases. Recently, we showed its time- and dose-

related therapeutic effect consisting in relief of neuropathic pain

caused by the mouse sciatic nerve chronic constriction injury, a

mononeuropathy model. We explored the genistein capacity to

attenuate diabetic neuropathic pain after its onset. The isoflavone

(3 and 6mg/kg, subcutaneously), once a day for 21 days, starting

two weeks after streptozotocin (STZ), relieved mechanical allodynia

in STZ-induced diabetic mice, without affecting hyperglycaemia

and body weight decrease. Hyperglycaemia leads to free radicals

generation, which consequently creates oxidative stress that is an

imbalance between radicalic and antioxidant compounds. Tissue

antioxidant status is a key factor in determining the deterioration

of diabetic stage and is important determinant of degenerative and

painful pathological conditions in peripheral nerve fibers. Genistein

increased the liver reduced glutathione, restored or increased the

activities of some antioxidant enzymes and decreased the ROS and

lipid peroxide overproduction in liver and brain. Hyperglycaemia

leads to cytokine control deregulation. The TNF-a, IL-1b and IL-6

overproduction in the sciatic nerve but not the TNF-a increase in

plasma of diabetic mice were reversed by genistein. These findings

suggested genistein ability to reverse diabetic neuropathic pain and

simultaneously to provide the protection against both oxidative

damage and peripheral nerve inflammation.

253

ANTI-HYPERALGESIC EFFECTS OF 5-HT7 RECEPTOR ACTIVATION

IN RATS SUFFERING FROM NEUROPATHIC PAIN: ROLE OF GABAA

RECEPTORS

F. Viguier1 *, B. Michot1, V. Kayser1, J.M. Vela2, M. Hamon1,

S. Bourgoin1. 1INSERM U894, UPMC, Faculte de Medecine Pierre

et Marie Curie, Site Pitie-Salpetriere, Paris, France; 2Labs Esteve,

Barcelona, Spain

Among receptors that mediate serotonin effects on acute

nociception, the 5-HT7 type (5-HT7R) is of special interest as it is

expressed by both dorsal root ganglion cells and intrinsic GABAergic

and opioidergic interneurons within the spinal dorsal horn, where

it mediates neuronal excitation. Herein, we investigated whether

5-HT7R may participate in some control of chronic pain in

neuropathic rats. Rats underwent unilateral constriction injury to

the sciatic nerve (CCISN), and the resulting allodynia/hyperalgesia

was assessed by determination of hindpaw pressure thresholds

(PT) to trigger ipsilateral paw withdrawal (PW) and vocalization

(V). Pharmacological treatments were performed two weeks after

CCISN, when allodynia/hyperalgesia had reached its maximum.

Significant decreases in PT to trigger PW (−30%) then V (−35%)

were noted in CCISN rats versus sham controls. Acute treatment

with the 5-HT7R antagonist SB269970 produced a limited (+30%)

and transient (80min) increase in PT. In contrast, the 5-HT7R

agonist E-55888 exerted marked antihyperalgesic effects that

could be prevented by SB269970. Furthermore, systemic and

intrathecal pretreatments with bicuculline (GABAA antagonist),

but not phaclofen (GABAB antagonist) or naloxone (opioidR

antagonist), significantly reduced the antihyperalgesic effects of

5-HT7R activation. These data suggest that, in neuropathic rats,

tonic activation of excitatory 5-HT7R (on primary afferent fibers)

by endogenous 5-HT contributes to hyperalgesia. In contrast,

strong 5-HT7R stimulation by a synthetic agonist produces

antihyperalgesic effects via GABAergic interneuron excitation

and subsequent GABAA stimulation. Spinal 5-HT7R appear as a

promising target for alleviating neuropathic pain.

254

COMBINED ANESTHESIA FOR NEFRECTOMY ON AN ATAXIA

WITH OCULOMOTOR APRAXIA TYPE2 PATIENT

C. Duarte*, J. Hidalgo. Centro Hospitalar do barlavento algarvio, EPE,

Portimao, Portugal

Ataxia with ocular motor apraxia type2 (AOA2) is an autosomal

recessive disorder characterised by cerebellar atrophy, axonal

sensory motor neuropathy, ocular motor apraxia and an elevated

alpha-fetoprotein serum concentration. Spinal/epidural anaesthesia

in patients with Friedreich’s ataxia or spinal cerebellar ataxia has

not been the subject of many studies. We report what we believe

to be the first case of combined anaesthesia (general and epidural)

in a patient with AOA2.

Clinical Features: 40-yr-old patient with clinical and family history

consistent with recessive hereditary autosomal transmission of

AOA2 planned for nephrectomy of a left renal tumour.

Anaesthetic procedure: Combined anaesthesia. Induction with

fentanyl, thiopental and atracurium; maintenance with sevoflurane

and atracurium. After the epidural L3-L4 negative test dose of 20mg

of lidocaine with adrenaline, a loading dose of 15mg of ropivacaine

and 3mg of morphine was administered and analgesia maintenance

was achieved with a mixture of ropivacaine 15mg and morphine

1mg. Post-operative pain was managed with an epidural DIB 48 h

(ropivacaine 150mg and morphine 4mg). The patient’s recovery

was uneventful and no subsequent neurological problems were

detected prior to discharge.

Conclusions: The use of central neuraxial blocks in patients with

multiple sclerosis is controversial and, although it has been used

safely, the unpredictable progression of neurological symptoms has

been observed. The decision to proceed with neuraxial anaesthesia

should be based on the pathophysiology and severity of each

case. The main advantage of using regional anaesthesia in patients

with hereditary peripheral neuropathies consists of eliminating

the triggers for malignant hyperthermia. Successful combined

anaesthesia was administered to a patient with a neurodegenerative

disease- AOA2- a demyelinating central and peripheral neuropathy.

255

EFFECTS OF LIDOCAINE ON ELECTRICALLY EVOKED COMPOUND

ACTION POTENTIALS IN RAT SCIATIC NERVE IN VITRO

L. Luo, A.B. Eriksson, P. Karila*. Molecular Pharmacology, AstraZeneca

R&D Sodertalje, Sodertalje, Sweden

Background and Aims: Local anesthetics, including lidocaine, at

subblocking concentrations produce tonic and phasic inhibition of

axonal excitability. The aim of the present study was to characterize

the inhibitory properties of lidocaine in rat peripheral nerves.

Methods: Rats were sacrificed by 100% CO2. Sciatic nerves were

dissected, put into a recording chamber and superfused with

synthetic interstitial fluid at 35ºC, pH 7.4 adjusted by 5% CO2–

95% O2. Lidocaine (15–300mM) was applied cumulatively on the

nerve. Electrical stimulus (0.09–0.6mA, 200ms for Aab-fibers and

0.3–1.5mA, 2ms for C-fibers) was delivered to the nerve 20 min

following lidocaine. Compound action potential (CAP) was recorded

via a suction electrode. The stimulation profile was 1 and 200Hz for

A-fibers, 0.2, 2, 5 and 10Hz for C-fibers, 10 pulses at 20 sec intervals.