Evidence that spinal segmental nitric oxide mediates tachyphylaxis to peripheral local anesthetic nerve block.

BACKGROUND: Tachyphylaxis to sciatic nerve blockade in rats correlates with hyperalgesia. Spinal inhibition of nitric oxide synthase with N(G)nitro-L-arginine methyl ester (L-NAME) has been shown to prevent hyperalgesia. Given systemically, L-NAME also prevents tachyphylaxis. The action of L-NAME in preventing tachyphylaxis therefore may be mediated at spinal sites. We compared systemic versus intrathecal potency of L-NAME in modulating tachyphylaxis to sciatic nerve block. METHODS: Rats were prepared with intrathecal catheters. Three sequential sciatic nerve blocks were placed. Duration of block of thermal nocifensive, proprioceptive and motor responses was recorded. We compared spinal versus systemic dose-response to L-NAME, and examined effects of intrathecal arginine on tachyphylaxis. An additional group of rats underwent testing after T10 spinal cord transection. In these rats duration of sciatic nerve block was assessed by determining the heat-induced flexion withdrawal reflex. RESULTS: L-NAME was 25-fold more potent in preventing tachyphylaxis given intrathecally than intraperitoneally. Intrathecal arginine augmented tachyphylaxis. Spinalized rats exhibited tachyphylaxis to sciatic block. CONCLUSION: The increased potency of intrathecal versus systemic L-NAME suggests a spinal site of action in inhibiting tachyphylaxis. Descending pathways are not necessary for the development of tachyphylaxis since it occurs even after T10 spinal cord transection. Thus tachyphylaxis, like hyperalgesia, is mediated at least in part by a spinal site of action.

Response properties and organization of nociceptive neurons in area 1 of monkey primary somatosensory cortex.

The organization and response properties of nociceptive neurons in area 1 of the primary somatosensory cortex (SI) of anesthetized monkeys were examined. The receptive fields of nociceptive neurons were classified as either wide-dynamic-range (WDR) neurons that were preferentially responsive to noxious mechanical stimulation, or nociceptive specific (NS) that were responsive to only noxious stimuli. The cortical locations and the responses of the two classes of neurons were compared. An examination of the neuronal stimulus-response functions obtained during noxious thermal stimulation of the glabrous skin of the foot or the hand indicated that WDR neurons exhibited significantly greater sensitivity to noxious thermal stimuli than did NS neurons. The receptive fields of WDR neurons were significantly larger than the receptive fields of NS neurons. Nociceptive SI neurons were somatotopically organized. Nociceptive neurons with receptive fields on the foot were located more medial in area 1 of SI than those with receptive fields on the hand. In the foot representation, the recording sites of nociceptive neurons were near the boundary between areas 3b and 1, whereas in the hand area, there was a tendency for them to be located more caudal in area 1. The majority of nociceptive neurons were located in the middle layers (III and IV) of area 1. The fact that nociceptive neurons were not evenly distributed across the layers of area 1 suggested that columns of nociceptive neurons probably do not exist in the somatosensory cortex. In electrode tracks where nociceptive neurons were found, approximately half of all subsequently isolated neurons were also classified as nociceptive. Low-threshold mechanoreceptive (LTM) neurons were intermingled with nociceptive neurons. Both WDR and NS neurons were found in close proximity to one another. In instances where the receptive field shifted, subsequently isolated cells were also classified as nociceptive. These data suggest that nociceptive neurons in area 1 of SI are organized in vertically orientated aggregations or clusters in layers III and IV.

NG-nitro-L-arginine methyl ester (L-NAME) prevents tachyphylaxis to local anesthetics in a dose-dependent manner.

A model of local anesthetic tachyphylaxis was developed in our group previously using repeated sciatic nerve blocks in rats. In this model, thermal hyperalgesia accelerated tachyphylaxis, and the noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, MK-801, prevented both hyperalgesia and tachyphylaxis. Nitric oxide is thought to be a second messenger for NMDA pathways in the spinal cord, and appears to be involved in spinal mechanisms of hyperalgesia. We hypothesized that nitric oxide synthase inhibitors would also inhibit the development of tachyphylaxis. Repeated rat sciatic nerve blocks were placed by percutaneous injection of 2-chloroprocaine. Block duration was tested by measuring hot-plate latency at 56 degrees C. Two hours before the first nerve block, rats received intraperitoneal injections with saline or one of six concentrations of NG-nitro-L-arginine methyl ester (L-NAME) in a randomized, blinded pattern. Control rats developed tachyphylaxis as seen previously: the duration of the third block was 30% that of the first. L-NAME inhibited the development of tachyphylaxis in a dose-dependent manner; tachyphylaxis was inhibited by 50% using L-NAME at 0.2mg/kg and completely abolished by 50 mg/kg. Nitric oxide pathways may be involved in the development of tachyphylaxis to local anesthetic nerve block.

Cadmium and lead residues in field-collected red swamp crayfish (Procambarus clarkii) and uptake by alligator weed, Alternanthera philoxiroides.

The whole-body residues of Cd and Pb in the tissues of Louisiana swamp crayfish (Procambarus clarkii) were determined by flame AAS technique. Test animals were collected from roadside ditches (18 locations) alongside major highways. The water and soil samples were also collected from the same sites. The mean Cd and Pb concentrations (mg/l) in crayfish tissues were 0.46 and 0.07, respectively. The levels of Cd and Pb in the water were 0.09 and 0.04; and in soil were 2.85 and 0.87 mg/l, respectively. The concentration of cadmium was 32 and Pb 12 times more than in the water. The bioaccumulation factors (BF) for Cd and Pb in crayfish tissues were 5.1 and 1.7, Alligator weed (Alternanthera philoxiroides) plants were exposed to 0.5 mg/l Cd-chloride or Pb-nitrate solutions for 3 wk period, thrice. The mean Pb accumulation in roots was 1.31 mg/l, followed by stem (0.078 mg/l), but Cd only accumulated in root (0.83 mg/l). The BF for Pb and Cd in plant tissues were 14.8 and 16.6, respectively. The uptake of metals was time-dependent (P = < 0.01). These data suggest that although there is no biomagnification of Cd and Pb from alligator weed to crayfish, both metals readily accumulate in field-collected crayfish and laboratory-exposed alligator weed.