Skin perfusion changes in experimental neuropathic pain: sciatic nerve constriction.

Laser Doppler flowmetry was used as a method of measurement of skin blood flow perfusion in an experimental rat model of neuropathic pain. The common sciatic nerve was microsurgically approached and four ligatures were loosely tied around the nerve (sciatic ligature group). Contralateral nerves were approached but not injured (sham procedure). All paws were studied before any surgical procedure (controls) and immediately, 24 h, 11 and 25 days after surgery. In each experiment, the skin perfusion was measured in the plantar surface of the hind paw, both in baseline conditions and after a heating test, where skin temperature around flowmeter probe reached 42 degrees C. The heating test produced an increase in skin perfusion that ranged between 70% and 80% in sham and normal paws. Nerve ligation induced no immediate changes in skin perfusion with a normal 65% increase after heating. However, 24 h later, baseline skin perfusion was significantly higher than preoperatively with smaller response to heating. This situation changed at 11 and 25 days, with baseline values significantly smaller than before surgery and responses to heating significantly higher. Nerve section in these previously ligated sciatic nerves produces a significant increase in skin perfusion. Our results suggest that vasomotor changes in the model of sciatic ligature are presumably related to a denervation hypersensitivity of skin blood vessels to vasoactive agents.

Skin perfusion changes after sciatic nerve transection in the rat.

Laser Doppler flowmetry was used as a method of measurement of skin blood flow perfusion in an experimental rat model of peripheral nerve section. The common sciatic nerve was microsurgically approached and cleanly severed (sciatic transection group). Contralateral nerves were approached but not injured (sham procedure). All paws were studied before any surgical procedure (controls) and immediately, 24 hours, 11 and 25 days after surgery. In each experiment, the skin perfusion was measured in the plantar surface of the hind paw, both in baseline conditions and after a heating test, where skin temperature around flowmeter probe reached 42 degrees C. Sham operated paws showed no differences from control unoperated paws. The heating test produced an increase in skin perfusion that ranged between 70% and 80% in sham and normal paws. Sciatic nerve section produces an immediate increase of 36.7% in blood flow with an additional increase of 27.5% after heating. In the following studies, on days 1, 11 and 25 baseline skin perfusion showed no changes in relation to preoperative values and heating induced only a small increase in perfusion.

Antinociceptive effects of phenobarbital in "tail-flick" test and deafferentation pain.

Deafferentation pain has been related to abnormal electrical hyperactivity in the neurons of the sensory relays in the central nervous system. This electrical activity resembles the epileptoid pattern observed in experimental epileptoid foci. With the aim of preventing this hyperactivity, rats were given long-term treatment with phenobarbital after sciatic transection and dorsal cervical rhizotomy. Daily intramuscular injections of saline solution or 5 and 10 mg/kg of phenobarbital were administered for 20 days, starting 10 days before surgery. Larger doses of phenobarbital delayed the onset and reduced the severity of autotomy. In a test of acute pain, the effect of intraperitoneal (1-16 mg) and intrathecal (100-500 micrograms) phenobarbital was studied by measuring the "tail-flick" response latency. Intraperitoneal phenobarbital did not modify acute pain, but 500 micrograms of intrathecal phenobarbital increased the threshold of pain. These results indicate that (a) phenobarbital, a drug with anticonvulsant activity, reduces deafferentation behavior in rats, and (b) intrathecal phenobarbital has an antinociceptive action in acute experimental pain.

Intrathecal antiepileptic drugs in experimental epilepsy.

The effect of intrathecal administration of antiepileptic drugs on electroshock-induced convulsions (maximal electroshock seizure, MES test) was investigated in an experimental study in rats. Drugs tested were phenobarbital sodium (50-800 micrograms), sodium valproate (50-6,400 micrograms) and midazolam (50-250 micrograms), delivered into the cerebrospinal fluid via a catheter placed in the upper cervical intrathecal space. Control animals were tested with saline. The animals were tested in the MES test 30 min after drug administration. Phenobarbital sodium showed a dose-related protective effect on the tonic phase of the convulsion, with a 50% effect at a dose of 200 micrograms. Sodium valproate showed a less protective effect, even when reaching doses that produced neurological symptoms. Midazolam protected at a high dose but produced a severe decrease in motor activity. The results indicate the feasibility to treat experimental convulsions by means of intrathecal injection of antiepileptic drugs.

[Analgesic and anticonvulsive effect of midazolam via intrathecal administration in the rat]. / Acción analgésica y anticonvulsionante del midazolam administrado por vía intratecal en la rata.

We have studied analgesic and anticonvulsive effect of midazolam by means of tail-flick test and electroshock respectively. The drug was administered via cervical and lumbar intrathecally in chronically implanted rats. Total doses were 50, 125, and 250 microg. Control animals received 0.3125, 0.625, 1.25 and 2.5 mg intraperitoneally. Degree of sedation was also measured with a motor activity scale with the purpose of correlating sedation with analgesic and anticonvulsive effect. Tail-flick test was carried out 5 and 30 minutes after the administration of midazolam. Results showed that lumbar intrathecal midazolam has analgesic effect in tail-flick test whereas cervical intrathecal or intraperitoneal midazolam has no analgesic effect and shows a non significant hyperalgesic trend. Cervical intrathecal and intraperitoneal midazolam has anticonvulsive effect. As sedative effect of the administered doses increases, there was also a not significant trend to shorten latency period of tail-flick test and to increase anticonvulsive effect.