Sensory Nerve Blockade Research Articles

Inhibition of Neuronal Apoptosis and Axonal Regression Ameliorates Sympathetic Atrophy and Hemodynamic Alterations in Portal Hypertensive Rats

Background and AimA neuronal pathway participates in the development of portal hypertension: blockade of afferent sensory nerves in portal vein ligated (PVL) rats simultaneously prevents brain cardiovascular regularory nuclei activation, neuromodulator overexpression in superior mesenteric ganglia, sympathetic atrophy of mesenteric innervation and hemodynamic alterations. Here we investigated in PVL rats alterations in neuromodulators and signaling pathways leading to axonal regression or apoptosis in the superior mesenteric ganglia and tested the effects of the stimulation of neuronal proliferation/survival by using a tyrosine kinase receptor A agonist, gambogic amide.ResultsThe neuronal pathway was confirmed by an increased neuronal afferent activity at the vagal nodose ganglia and the presence of semaphorin3A in sympathetic pre-ganglionic neurons at the intermediolateral nucleus of the spinal cord of PVL rats. Expression of the active form of tyrosine kinase receptor A (phosphorylated), leading to proliferation and survival signaling, showed a significant reduction in PVL comparing to sham rats. In contrast, the apoptotic and axonal retraction pathways were stimulated in PVL, demonstrated by a significant overexpression of semaphorin 3A and its receptor neuropilin1, together with increases of cleaved caspase7, inactive poly(ADP-ribose) polymerase and Rho kinase expression. Finally, the administration of gambogic amide in PVL rats showed an amelioration of hemodynamic alterations and sympathetic atrophy, through the activation of survival pathways together with the inhibition of apoptotic cascades and Rho kinase mediated axonal regression.ConclusionThe adrenergic alteration and sympathetic atrophy in mesenteric vessels during portal hypertension is caused by alterations on neuromodulation leading to post-ganglionic sympathetic regression and apoptosis and contributing to splanchnic vasodilation.

Lateral Trendelenburg with the injected side down after the block improves the efficacy of the axillary approach to brachial plexus block

We hypothesized that, after axillary block, positioning the patient in a lateral position with the injected side down and simultaneously in a 20° Trendelenburg position will increase the success rate and quality of the block. Fifty patients with chronic renal failure (ASA 2-3) scheduled for arteriovenous fistula surgery were included in this study. In all patients, 30-40 ml of 0.25 % levobupivacaine were injected into the axillary sheath. The block was performed as three injections (multiple injection technique) with the arm in 90° abduction and 90° flexion in the supine position. Patients were randomly allocated to two groups. Group I (n = 25) patients were kept in the supine position after the block. Group II (n = 25) patients were positioned laterally after the block with the injected arm down and in a 20° Trendelenburg position. Sensory and motor block were evaluated at 2, 4, 6, 8, 10, 15, 20, and 25 min after the administration of the block. Thus, the patients in group II were evaluated in a lateral position during the first 30 min. Throughout the surgery and the recovery period, sensory and motor block were evaluated at 30-min intervals. There were no significant intergroup differences in the effects on radial, ulnar, median, and musculoskeletal nerve blockade. Thirty minutes after the injection, the patients in group II had higher levels of sensory axillary nerve blockade. Subscapular and thoracodorsal nerve motor block were not detected in group I, while 84 % of the patients in group II experienced blockade of both of these nerves (p < 0.01). We conclude that, for patients undergoing an axillary block, positioning the patient laterally with the injected side down and in a 20° Trendelenburg position increases the success rate and quality of the block.

Role of sensory nerves in the rapid cutaneous vasodilator response to local heating in young and older endurance-trained and untrained men

The ability to increase skin blood flow (SkBF) rapidly in response to local heating is diminished with advanced age; however, the mechanisms are unclear. The primary aim of this study was to investigate the role of sensory nerves in this age-related change. A secondary aim was to investigate the effect of aerobic fitness on sensory nerve-mediated vasodilatation in young and aged skin. We measured SkBF (using laser Doppler flowmetry) in young and older endurance-trained and untrained men (n= 7 in each group) at baseline and during 35 min of local skin heating to 42°C at two sites on the ventral forearm. One site was pretreated with topical anaesthetic cream to block local sensory nerve function. Cutaneous vascular conductance (CVC) was calculated as SkBF divided by mean arterial pressure and normalized to maximal values (CVC(max)) achieved during local heating to 44°C. At the untreated site, the rapid vasodilatation during the first ~5 min of local heating (initial peak) was lower in the older untrained group (68 ± 3%CVC(max)) compared with all other groups (young trained, 76 ± 4%CVC(max); young untrained, 75 ± 5%CVC(max); and older trained, 81 ± 3%CVC(max); P < 0.05). Sensory nerve blockade abolished these differences among the groups (P > 0.05). The contribution of sensory nerve-mediated vasodilatation was lower in the older untrained group compared with all other groups (P< 0.05). Our results suggest that the age-related decline in the rapid vasodilator response to local heating in human skin is explained by diminished sensory nerve-mediated vasodilatation. These findings also indicate that this age-related change can be prevented through participation in regular aerobic exercise.

Poly(dl:Lactic Acid-Castor Oil) 3:7-Bupivacaine Formulation: Reducing Burst Effect Prolongs Efficacy In Vivo

Prolonged analgesia may be achieved using a single injection of slow-release local anesthetic formulation. The study objective was to improve the efficacy of a previously reported formulation comprising 10% bupivacaine in poly(DL:lactic acid co castor oil) 3:7. The polymer was loaded with 15% bupivacaine and injected through a 22G needle close to the sciatic nerve of ICR mice. Sensory and motor nerve blockade were measured. The efficacy and toxicity of the polymer-drug combination were determined. Sixty percent of the incorporated bupivacaine was released during 1 week in vitro. During in vitro release no burst effect was seen, suggesting low toxicity of the formulation. Single injection of 0.1 mL of 15% polymer-bupivacaine formulation caused motor block that lasted 64 h and sensory block that lasted 96 h. The MTD of the polymer-drug formulation was established as 0.175 mL. Microscopic examination of the injection sites revealed reversible nerve inflammation and normal internal organs. The polymer poly(DL:lactic acid co castor oil) 3:7 is a safe carrier for prolonged activity of bupivacaine up to 96 h. The increase of drug load in the formulation reduces the drug release rates due to stronger polymer-drug interactions and higher overall hydrophobicity of the formulation.

Blockade of airway sensory nerves and dyspnea in humans

Evidence has accumulated from previous studies that vagal fibers in the lungs are involved in the genesis of dyspnea. In a series of human studies, based on our previous animal data (J Physiol 1998; 508:109–18; J Appl Physiol 1998; 84:417–24; J Appl Physiol 2003; 95:1315–24) we established that intravenous adenosine has a dyspnogenic effect (J Appl Physiol 2005; 98:180–5; Respir Res 2006; 7:139; Pulm Pharmacol Ther 2008; 21:208–13), strongly implicating a role for vagal C-fibers in the genesis of dyspnea. We have now analyzed the relative effects of blockade of vagal C-fibers by two methods and routes of delivery: by inhibition of the sodium channel and interruption of action potential conduction in the nerve by inhaled local anesthetic (lidocaine), and by blockade by systemic theophylline, a known, nonselective adenosine receptor antagonist. Both techniques significantly ( p < 0.05) attenuated the dyspneic response to intravenous adenosine. However, the attenuation was significantly ( p < 0.05) greater with pretreatment with systemic theophylline (mean change in response, ΔAUC −44%) versus pretreatment with inhaled lidocaine (mean change in response, ΔAUC −11.8%). These differences in the results of airway sensory nerve blockade probably reflect different populations of C fiber receptors and may explain conflicting results of previous studies of dyspnea and airway anesthesia.

Peribulbar anesthesia for cataract surgery: effect of lidocaine warming and alkalinization on injection pain, motor and sensory nerve blockade.

Aim:To compare self-reported pain and efficacy of warmed, alkalinized, and warmed alkalinized lidocaine with plain 2% lidocaine at room temperature for peribulbar anesthesia in cataract surgery.Materials and Methods:Through a prospective, single-blinded, randomized, controlled clinical trial 200 patients were divided into four groups. They received either lidocaine at operating room temperature 18°C, control group (Group C), lidocaine warmed to 37°C (Group W), lidocaine alkalinized to a pH of 7.09 ± 0.10 (Group B) or lidocaine at 37°C alkalinized to a pH of 6.94 ± 0.05 (Group WB). All solutions contained Inj. Hyaluronidase 50 IU/ml. Pain was assessed using a 10-cm visual analog score scale. Time of onset of sensory and motor blockade and time to onset of postoperative pain were recorded by a blinded observer.Results:Mean pain score was significantly lower in Group B and WB compared with Group C (P < 0.001). Onset of analgesia was delayed in Group C compared with Group B (P = 0.021) and WB (P < 0.001). Mean time taken for the onset of complete akinesia and supplementation required for the block was significantly lower in Group B. Time of onset of pain after operation was significantly earlier in Group W compared with Group C (P = 0.036).Conclusion:Alkalinized lidocaine with or without warming produced less pain than lidocaine injected at room temperature. Alkalinization enhances the effect of warming for sensory nerve blockade, but warming does not enhance alkalinization, in fact it reduces the efficacy of alkalinized solution for blocking the motor nerves in the eye.

Prolonged Local Anesthetic Action Through Slow Release from Poly(Lactic Acid Co Castor Oil)

To evaluate a new formulation of bupivacaine loaded in an injectable fatty acid based biodegradable polymer poly(lactic acid co castor oil) in prolonging motor and sensory block when injected locally. The polyesters were synthesized from DL: -lactic acid and castor oil with feed ratio of 4:6 and 3:7 w/w. Bupivacaine was dispersed in poly(fatty ester) liquid and tested for drug release in vitro. The polymer p(DLLA:CO) 3:7 loaded with 10% bupivacaine was injected through a 22G needle close to the sciatic nerve of ICR mice and the duration of sensory and motor nerve blockade was measured. The DL: -lactic acid co castor oil p(DLLA:CO) 3:7 released 65% of the incorporated bupivacaine during 1 week in vitro. Single injection of 10% bupivacaine loaded into this polymer caused motor block that lasted 24 h and sensory block that lasted 48 h. Previously we developed a ricinoleic acid based polymer with incorporated bupivacaine which prolonged anesthesia to 30 h. The new polymer poly(lactic acid co castor oil) 3:7 provides slow release of effective doses of the incorporated local anesthetic agent and prolongs anesthesia to 48 h.

Abnormal digital neurovascular response to local heating in systemic sclerosis

To investigate neurovascular dysfunction using the axon reflex-dependent hyperaemia (initial peak of skin local heating response) in fingers of patients with SSc or primary RP. Ten healthy subjects were initially enrolled to compare axon reflex-dependent thermal hyperaemia between the finger and forearm cutaneous circulations. Then, 10 patients with primary RP and 16 patients with SSc participated in a similar protocol focusing on the finger circulation only. Lidocaine/prilocaine cream was applied for 1 h to produce local blockade of cutaneous sensory nerves. After lidocaine/prilocaine pre-treatment, laser Doppler probes were heated from skin temperature to 42 degrees C for 30 min, and 44 degrees C for 5 min to achieve maximal skin blood flow. Data were expressed as a percentage of maximal cutaneous vascular conductance. In healthy volunteers, we observed a significantly higher initial peak on the finger compared with the forearm, with both responses blunted following topical anaesthesia. In primary RP patients, we observed a decreased initial peak following lidocaine/prilocaine pre-treatment in the finger circulation [96.7% (33.4) vs 75.9% (29.5) with anaesthesia, P = 0.02]. In contrast, pre-treatment did not alter the initial peak in patients with SSc. A minute-by-minute analysis showed no delay of the initial peak. We show an abnormal digital neurovascular response to local heating in SSc. Thermal hyperaemia could be monitored as a clinical test for neurovascular function in SSc. Further studies are required to test whether the abnormal digital neurovascular response correlates to the degree of peripheral vascular involvement.

Mechanisms of vasoconstriction with direct skin cooling in humans

direct skin cooling causes a vasoconstriction partly dependent on α2-adrenergic function. In in vitro studies, this is a manifestation of reactive oxygen species stimulating Rho and Rho kinase to cause translocation of α2C-receptors from the Golgi to the plasma membrane. In this issue of American

Long acting local anesthetic–polymer formulation to prolong the effect of analgesia

Prolonged postoperative analgesia cannot be achieved using single injections of local anesthetic solutions. The study objective was to evaluate the efficacy and toxicity of a new formulation of bupivacaine loaded in an injectable fatty acid based biodegradable polymer poly(sebacic-co-ricinoleic acid) for producing motor and sensory block when injected near the sciatic nerve. Bupivacaine was dissolved in poly(fatty ester-anhydride) paste and tested for drug release in vitro and in vivo after injection in mice. The efficacy and toxicity of the polymer–drug combination was determined by injecting the polymer formulation near the sciatic nerve of mice and measure the sensory and motor nerve blockade for 48 h, while monitoring the animal general health and the injection site. Seventy percent of the incorporated drug was released during 1 week in vitro. Single injection of 10% bupivacaine in the polymer caused motor and sensory block that lasted 30 h. Microscopic examination of the injection sites revealed only mild infiltration in three of eight examined tissues with no pathological findings for internal organs were found. In conclusion the polymer poly(sebacic-co-ricinoleic acid) is a safe carrier for prolonged activity of bupivacaine.

Sympathetic, sensory, and nonneuronal contributions to the cutaneous vasoconstrictor response to local cooling

Previous work indicates that sympathetic nerves participate in the vascular responses to direct cooling of the skin in humans. We evaluated this hypothesis further in a four-part series by measuring changes in cutaneous vascular conductance (CVC) from forearm skin locally cooled from 34 to 29 degrees C for 30 min. In part 1, bretylium tosylate reversed the initial vasoconstriction (-14 +/- 6.6% control CVC, first 5 min) to one of vasodilation (+19.7 +/- 7.7%) but did not affect the response at 30 min (-30.6 +/- 9% control, -38.9 +/- 6.9% bretylium; both P < 0.05, P > 0.05 between treatments). In part 2, yohimbine and propranolol (YP) also reversed the initial vasoconstriction (-14.3 +/- 4.2% control) to vasodilation (+26.3 +/- 12.1% YP), without a significant effect on the 30-min response (-26.7 +/- 6.1% YP, -43.2 +/- 6.5% control; both P < 0.05, P > 0.05 between sites). In part 3, the NPY Y1 receptor antagonist BIBP 3226 had no significant effect on either phase of vasoconstriction (P > 0.05 between sites both times). In part 4, sensory nerve blockade by anesthetic cream (Emla) also reversed the initial vasoconstriction (-20.1 +/- 6.4% control) to one of vasodilation (+213.4 +/- 87.0% Emla), whereas the final levels did not differ significantly (-37.7 +/- 10.1% control, -37.2 +/- 8.7% Emla; both P < 0.05, P > 0.05 between treatments). These results indicate that local cooling causes cold-sensitive afferents to activate sympathetic nerves to release norepinephrine, leading to a local cutaneous vasoconstriction that masks a nonneurogenic vasodilation. Later, a vasoconstriction develops with or without functional sensory or sympathetic nerves.

Nitric oxide-releasing aspirin protects gastric mucosa against ethanol damage in rats with functional ablation of sensory nerves.

The aim of the present study was to investigate, whether sensory nerves are involved in the gastroprotection induced by NO releasing non-steroidal anti-inflammatory drugs (NO-NSAID). Studies were performed in Wistar rats with intact or inactivated sensory nerves by pretreatment with large dose of capsaicin (125 mg/kg sc). Acute gastric lesions were induced by 100% ethanol (100% EtOH). 1 h before exposure to 100% EtOH, rats received vehicle, aspirin (ASA) or NO-releasing aspirin (NO-ASA) in the same dose (50 mg/kg). The animals were killed 1 h after exposure to 100% EtOH. Determinations were made of gastric mucosal injury, mucosal gastric blood flow, mucosal mRNA expression of glutathione peroxidase (GPx), zinc copper superoxide dismutase (SOD) and heat shock protein (HSP70) by RT-PCR and protein expression for HSP70 by Western blotting. Pretreatment with ASA aggravated the acute gastric injury induced by 100% EtOH, whereas pretreatment with NO-ASA led to a significant reduction in this injury. Administration of 100% EtOH was accompanied by a pronounced upregulation of HSP70, which was reduced by ASA, but enhanced by NO-ASA application. Sensory deactivation with capsaicin enhanced acute ethanol lesions and led to a significant attenuation in HSP70 expression. In contrast to ASA, NO-ASA attenuated gastric mucosal lesions and significantly upregulated HSP70 expression despite blockade of sensory nerves. NO-ASA, but not ASA, caused an upregulation of SOD and GPx mRNA in gastric mucosa with or without sensory denervation. NO-ASA protects gastric mucosa even after blockade of sensory nerves due to the upregulation of HSP70 expression and attenuation of the oxidative injury resulting from strong upregulation of genes for antioxidant enzymes.

Evaluation of Differential Cutaneous Sensory Nerve Blockade with Lioposomal Lidocaine Using Non-Noxious Neuroselective Electrostimulation

Evaluation of Differential Cutaneous Sensory Nerve Blockade with Lioposomal Lidocaine Using Non-Noxious Neuroselective Electrostimulation

Sciatic nerve blockade with lipid-protein-sugar particles containing bupivacaine.

To assess the efficacy of lipid-protein-sugar particles (LPSPs) in providing prolonged duration local anesthesia by percutaneous injection. Bupivacaine-containing LPSPs were characterized and optimized in vitro. Male Sprague-Dawley rats were given sciatic nerve blocks with bupivacaine-containing LPSPs. Sensory and motor nerve blockade were measured in the hindpaw, as were contralateral functional deficits (a measure of systemic drug distribution). Poly(lactic-co-glycolic) acid (PLGA) microspheres were used as a reference. 10% (w/w) bupivacaine LPSPs (60% dipalmitoylphosphatidylcholine) were 4.4+/-0.39 microm in diameter, with a tap density of 0.11 +/-0.04 g/ml. These LPSPs and 50% (w/w) PLGA microspheres had comparable durations of sensory blockade (468+/-210 min vs. 706+/-344 min, p = 0.08), although the LPSPs produced a much lesser duration of motor blockade (508+/-258 min vs. 1062+/-456 min, p = 0.005). Systemic toxicity was minimal in both groups. LPSPs provide sensory blockade durations comparable to those from PLGA microspheres, with a smaller amount of drug loading. Motor blockade is shorter with LPSPs than with PLGA microspheres. LPSPs appear to be suitable for extended nerve blockade. Given their size and low density, they may be useful for topical anesthesia of the airway.

Leptin in gastroprotection induced by cholecystokinin or by a meal. Role of vagal and sensory nerves and nitric oxide

Leptin, detected recently in the stomach, is a product of the ob gene released by cholecystokinin (CCK) and plays an important role in the control of food intake but its influence on gastroprotection against the damage caused by noxious agents has not been studied. This study was designed to compare the effects of leptin and cholecystokinin-8 (CCK-8) on gastric mucosal lesions induced by topical application of 75% ethanol or acidified aspirin. Four series of Wistar rats (A, B, C and D) were used to determine the effects of: (A) suppression of prostaglandin biosynthesis by indomethacin (5 mg/kg i.p.); (B) inhibition of nitric oxide (NO)-synthase by nitro- l-arginine methyl ester ( l-NAME) (5 mg/kg i.v.); (C) blockade of sensory nerves by capsaicin (125 mg/kg s.c.) and (D) bilateral vagotomy, on the gastric lesions induced by intragastric (i.g.) application of ethanol with or without pretreatment with CCK-8, a known gastroprotective substance or leptin. CCK-8 (1–100 μg/kg i.p.) and leptin (0.1–50 μg/kg i.p.) dose dependently attenuated gastric lesions induced by 75% ethanol; the dose reducing these lesions by 50% being about 10 μg/kg and 8 μg/kg, respectively. The protective effects of CCK-8 and leptin were accompanied by a significant rise in gastric blood flow (GBF) and luminal NO concentration. Leptin was also effective to attenuate aspirin-induced damage and the accompanying fall in the GBF, whereas CCK-8 dose dependently worsened aspirin damage and failed to influence GBF. CCK (1–100 μg/kg i.p.), given in graded doses, produced a dose-dependent increase in the plasma leptin level and a rise of the expression of ob messenger RNA (mRNA) in gastric mucosa, the maximum being reached at a dose of 100 μg/kg. Pretreatment with CCK-8 (10 μg/kg i.p.) or with 8% peptone, that is known to stimulate CCK release, also produced a significant rise in plasma leptin levels and up-regulation of ob mRNA while reducing significantly the gastric lesions induced by 75% ethanol to the same extent as that induced by exogenous leptin (10 μg/kg i.p.). Indomethacin, which suppressed prostaglandin generation by ∼90%, failed to influence leptin- or CCK-8-induced protection against ethanol, whereas l-NAME attenuated significantly CCK-8- and leptin-induced protection and hyperemia but addition to l-NAME of l-arginine, but not d-arginine, restored the protective and hyperemic effects of both hormones. The ob mRNA was detected as a weak signal in the intact gastric mucosa and in that exposed to ethanol alone but this was further enhanced after treatment with graded doses of CCK-8 or peptone meal applied prior to ethanol. We conclude that: (1) exogenous leptin or that released endogenously by CCK or meal exerts a potent gastroprotective action depending upon vagal activity, and involving hyperemia probably mediated by NO and sensory nerves but unrelated to endogenous prostaglandins; (2) leptin mimics the gastroprotective effect of CCK and probably mediates the protective and hyperemic actions of CCK in the rat stomach.

Involvement of endogenous cholecystokinin and somatostatin in gastroprotection induced by intraduodenal fat.

Duodenal fat such as oleate is known to influence gut functions by release of cholecystokinin (CCK), but the contribution of CCK endogenously released by duodenal fat or by diversion of pancreatic juice from the duodenum in the mechanism of mucosal integrity and gastroprotection has been little studied. This study was designed to compare the effect of CCK-8 and intraduodenal (i.d.) instillation of sodium oleate, or diversion of the pancreatic biliary secretions that are known to release CCK, on the gastric mucosal lesions induced by topical application of 100% ethanol or acidified aspirin (ASA) in rats with or without the pretreatment with a CCK-A receptor antagonist, loxiglumide, or with L-365,260 to block CCK-B receptors. In addition, the effect of suppression of prostaglandin (PG) biosynthesis by indomethacin (5 mg/kg i.p.), inhibition of nitric oxide (NO)-synthase by L-NAME (5 mg/kg i.v.), or blockade of sensory nerves by capsaicin (125 mg/kg s.c.) on the protective activity of sodium oleate was determined. Sodium oleate (50-200 mM i.d.), or diversion of pancreatic juice from the duodenum for 3 h that produced significant rise in plasma CCK levels, significantly reduced gastric lesions induced by 100% ethanol to an extent similar to that induced by exogenous CCK-8 (5 nmol/kg s.c.). The protective effect of oleate or diversion of pancreatic juice was accompanied by an increase in gastric blood flow (GBF). Both protection and accompanying hyperemia were completely abolished by blockade of CCK-A receptors with loxiglumide, whereas L-365,260, an antagonist of CCK-B receptors, had no effect. Oleate given i.d. significantly attenuated acidified ASA-induced gastric lesions and gastric secretion while increasing the luminal concentration of somatostatin. These effects were significantly reduced by loxiglumide but not by L-365,260. In contrast, CCK-8, which stimulated gastric acid secretion, failed to affect the lesions induced by acidified ASA and the decrease in the GBF produced by this ulcerogen. Indomethacin, which suppressed PG generation by approximately 90%, failed to influence the protective activity of oleate or CCK-8 against ethanol-induced lesions, whereas L-NAME, vagotomy, or sensory denervation significantly attenuated this protection and accompanying hyperemia. Addition to L-NAME of L-arginine, but not D-arginine, restored the protective and hyperemic effects of CCK-8 and duodenal oleate against gastric lesions induced by ethanol or acidified ASA. We conclude that endogenous CCK released by oleate or diversion of pancreatic secretion exerts a potent gastroprotective action on the stomach involving predominantly CCK-A receptors and depending on vagal activity, and hyperemia mediated by NO and sensory nerves but unrelated to acid secretory effects and endogenous PG.

Natural killer cell response to exercise in humans: effect of hypoxia and epidural anesthesia

For the response of immunologically competent blood cells to exercise, the importance of afferent nerve impulses was evaluated. On separate days, seven males cycled in a recumbent position approximately 60% of maximal O2 uptake with and without sensory nerve blockade by lumbar epidural anesthesia. Blood samples were collected after 60 min of rest, 20 min of exercise, and 120 min postexercise. Subsequently, on each day, the subjects were exposed to 11.5% O2-88.5% N2 for 10 min. This was followed by 20 min of hypoxic exercise at the same work rate, and a final blood sample was obtained. The concentrations of lymphocytes expressing the cluster designation (CD) cell-surface antigens CD3, CD4, CD8, and CD14 became elevated during exercise, and these responses were enhanced by hypoxia (P < or = 0.01). The most pronounced changes were within the concentrations of CD16+ and CD56+ natural killer cells, which increased twofold during normoxic and fivefold during hypoxic exercise (P < or = 0.01). Sensory nerve blockade decreased the number of CD3+ and CD4+ cells and increased the percentage of CD16+ cells, independent of exercise and hypoxia (P < or = 0.05). Sensory nerve blockade caused minor enhancement in the increase of unstimulated natural killer cell activity during exercise (P = 0.07) and enhanced the interferon-alpha-stimulated activity at normoxia (P < or = 0.05), whereas no effect was detected at hypoxia. The results demonstrate that the responses of immunological competent cells to normoxic and hypoxic exercise are not abolished by blockade of nerve impulses from active muscle.

Modulation of sympathetic nerve activity during posthandgrip muscle ischemia in humans

To evaluate modulation of muscle sympathetic nerve activity (MSNA) during posthandgrip muscle ischemia (PHGMI), subjects performed 2 min of isometric handgrip at 33% of maximal voluntary contraction (MVC) followed by 2 min of PHGMI produced by forearm vascular occlusion. The response to PHGMI was studied in the absence and again during the addition of contralateral rhythmic handgrip (RHG; 40 times/min) at 15% (n = 6) and 30% (n = 10) MVC during the second minute of the PHGMI. Additionally, to isolate the effect of central command, response to PHGMI was studied during attempted RHG after sensory nerve blockade (n = 5). RHG for 2 min at 15 and 30% MVC and attempted RHG for 2 min did not increase MSNA. Isometric handgrip elicited an 130 +/- 48% increase in MSNA (P < 0.05), which was maintained during PHGMI. RHG at 15 and 30% MVC elicited an attenuation of MSNA (-10 +/- 7% and -14 +/- 6%, respectively) when performed during the second minute of PHGMI (P < 0.05). In contrast, attempted RHG did not significantly affect MSNA during PHGMI. The findings demonstrate modulation of MSNA during activation of the muscle metaboreflex. The attenuation of metaboreceptor-mediated increases in MSNA appear to be the result of mechanosensitive muscle afferents and not central command.

Can a super-imposed maximal voluntary contraction be as effective as a complete sensory nerve blockade in reducing pain associated with electrically evoked muscle contractions?

Can a super-imposed maximal voluntary contraction be as effective as a complete sensory nerve blockade in reducing pain associated with electrically evoked muscle contractions?

Recovery of function after cryosurgical lesions of peripheral nerves in rats

Unilateral lesions were made in rat sciatic nerves with a cryoprobe at about −65°C. Three months later, recovery of motor and sensory function of the hindlimb had occurred. The compound action potential from the dorsal root indicated that myelinated and unmyelinated fibre groups had regenerated. Cryosurgery may be useful in the long-term blockade of sensory nerves for pain relief.