A topographical and physiological exploration of C-tactile afferents and their response to menthol and histamine.

Unmyelinated tactile (C-tactile or CT) afferents are abundant in arm hairy skin and have been suggested to signal features of social affective touch. Here, we recorded from unmyelinated low-threshold mechanosensitive afferents in the peroneal and radial nerves. The most distal receptive fields were located on the proximal phalanx of the third finger for the superficial branch of the radial nerve and near the lateral malleolus for the peroneal nerve. We found that the physiological properties with regard to conduction velocity and mechanical threshold, as well as their tuning to brush velocity, were similar in CT units across the antebrachial (n = 27), radial (n = 8), and peroneal (n = 4) nerves. Moreover, we found that although CT afferents are readily found during microneurography of the arm nerves, they appear to be much more sparse in the lower leg compared with C-nociceptors. We continued to explore CT afferents with regard to their chemical sensitivity and found that they could not be activated by topical application to their receptive field of either the cooling agent menthol or the pruritogen histamine. In light of previous studies showing the combined effects that temperature and mechanical stimuli have on these neurons, these findings add to the growing body of research suggesting that CT afferents constitute a unique class of sensory afferents with highly specialized mechanisms for transducing gentle touch.NEW & NOTEWORHY Unmyelinated tactile (CT) afferents are abundant in arm hairy skin and are thought to signal features of social affective touch. We show that CTs are also present but are relatively sparse in the lower leg compared with C-nociceptors. CTs display similar physiological properties across the arm and leg nerves. Furthermore, CT afferents do not respond to the cooling agent menthol or the pruritogen histamine, and their mechanical response properties are not altered by these chemicals.

Functional characterization of a second pedal peptide/orcokinin-type neuropeptide signaling system in the starfish Asterias rubens.

Molluscan pedal peptides (PPs) and arthropod orcokinins (OKs) are prototypes of a family of neuropeptides that have been identified in several phyla. Recently, starfish myorelaxant peptide (SMP) was identified as a PP/OK-type neuropeptide in the starfish Patiria pectinifera (phylum Echinodermata). Furthermore, analysis of transcriptome sequence data from the starfish Asterias rubens revealed two PP/OK-type precursors: an SMP-type precursor (A. rubens PP-like neuropeptide precursor 1; ArPPLNP1) and a second precursor (ArPPLNP2). We reported previously a detailed analysis of ArPPLNP1 expression in A. rubens and here we report the first functional characterization ArPPLNP2-derived neuropeptides. Sequencing of a cDNA encoding ArPPLNP2 revealed that it comprises eleven related neuropeptides (ArPPLN2a-k), the structures of several of which were confirmed using mass spectrometry. Analysis of the expression of ArPPLNP2 and neuropeptides derived from this precursor using mRNA in situ hybridization and immunohistochemistry revealed a widespread distribution, including expression in radial nerve cords, circumoral nerve ring, digestive system, tube feet and innervation of interossicular muscles. In vitro pharmacology revealed that the ArPPLNP2-derived neuropeptide ArPPLN2h has no effect on the contractility of tube feet or the body wall-associated apical muscle, contrasting with the relaxing effect of ArPPLN1b (ArSMP) on these preparations. ArPPLN2h does, however, cause dose-dependent relaxation of cardiac stomach preparations, with greater potency/efficacy than ArPPLN1b and with similar potency/efficacy to the SALMFamide neuropeptide S2. In conclusion, there are similarities in the expression patterns of ArPPLNP1 and ArPPLNP2 but our data also indicate specialization in the roles of neuropeptides derived from these two PP/OK-type precursors in starfish.

Medium-latency reflex response elicited from the flexor carpi radialis by radial nerve stimulation.

The H reflex obtained from the flexor carpi radialis muscle by median nerve stimulation is a well-known monosynaptic reflex. However, the origin of the late responses is still contentious. Radial nerve stimulation was performed through the spiral groove, and EMG recording was obtained from the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles. An M response followed by an F response was achieved from the ECR by radial nerve stimulation; the antagonistic FCR muscle elicited a late response. A total of 25 cases were included in this study. In 22 of these cases, a response with a latency of 40.97 ± 5.35 ms was obtained from the FCR by radial nerve stimulation. When extension of the hand was restricted, the response disappeared in five of nine cases. Application of cold markedly suppressed the response and prolonged the latency of the FCR medium-latency reflex response (FCR-MLR). Oral tizanidine considerably suppressed the FCR-MLR response. Two out of eight cases did not exhibit any response. No response could be recorded from a patient with complete amputation of the right hand. The FCR-MLR is the reflex caused by stretching of the FCR muscle from radial nerve stimulation, and it is greatly influenced by group II afferents.

Continuous peripheral nerve block in forearm for severe hand trauma.

We studied the use of a continuous peripheral nerve block (CPNB) in the distal forearm and wrist immediately after emergent surgery for severe hand trauma in 22 hands. After emergent surgery, a 2-3 cm longitudinal incision was made at the distal forearm and an 18-gauge catheter was inserted along the peripheral nerves. All patients received postoperative analgesia by continuous infusion of 0.2% ropivacaine at 2 ml/h for seven to 21 days. Pain score remained low during postoperative period and only a small number of analgesic rescues were needed. There were no major complications related to the CPNB and one patient showed mild superficial infection at the insertion site that immediately recovered after catheter removal. This method provides good postoperative analgesia without loss of motor function in extrinsic hand muscles and should be considered as a postoperative pain management for severe hand trauma.

Non-redundant function of dystroglycan and ß1 integrins in radial sorting of axons.

Radial sorting allows the segregation of axons by a single Schwann cell (SC) and is a prerequisite for myelination during peripheral nerve development. Radial sorting is impaired in models of human diseases, congenital muscular dystrophy (MDC) 1A, MDC1D and Fukuyama, owing to loss-of-function mutations in the genes coding for laminin α2, Large or fukutin glycosyltransferases, respectively. It is not clear which receptor(s) are activated by laminin 211, or glycosylated by Large and fukutin during sorting. Candidates are αß1 integrins, because their absence phenocopies laminin and glycosyltransferase deficiency, but the topography of the phenotypes is different and ß1 integrins are not substrates for Large and fukutin. By contrast, deletion of the Large and fukutin substrate dystroglycan does not result in radial sorting defects. Here, we show that absence of dystroglycan in a specific genetic background causes sorting defects with topography identical to that of laminin 211 mutants, and recapitulating the MDC1A, MDC1D and Fukuyama phenotypes. By epistasis studies in mice lacking one or both receptors in SCs, we show that only absence of ß1 integrins impairs proliferation and survival, and arrests radial sorting at early stages, that ß1 integrins and dystroglycan activate different pathways, and that the absence of both molecules is synergistic. Thus, the function of dystroglycan and ß1 integrins is not redundant, but is sequential. These data identify dystroglycan as a functional laminin 211 receptor during axonal sorting and the key substrate relevant to the pathogenesis of glycosyltransferase congenital muscular dystrophies.

Evaluation of a midhumeral block of the radial, ulnar, musculocutaneous and median (RUMM block) nerves for analgesia of the distal aspect of the thoracic limb in dogs.

OBJECTIVE: To evaluate a technique for midhumeral peripheral nerve blockade in the dog. STUDY DESIGN: Cadaveric technique development; in vivo placebo-controlled, prospective crossover study. ANIMALS: Canine cadavers (n=38) and 8 clinically healthy, adult hound dogs. METHODS: A technique for peripheral block of the radial, ulnar, musculocutaneous, and median nerves (RUMM block) was evaluated using cadaver limbs. Eight purpose-bred, research dogs were anesthetized; a RUMM block was performed on each thoracic limb. One limb from each dog randomly received 0.5% bupivacaine and the opposite limb was assigned to receive sterile saline solution as a control. After recovery from anesthesia, skin sensation at selected dermatomes was evaluated for 24 hours using a mechanical stimulus. Weight-bearing, conscious proprioception, and withdrawal reflex were also evaluated. One month after initial testing, each dog was reanesthetized and each limb received the opposite treatment. RESULTS: Sensory thresholds were significantly increased over baseline measurements when compared with control limbs for all nerves. Complete sensory block was achieved in radial (15/16), ulnar (3/16), musculocutaneous (8/16), and median (11/16) nerves, using a mechanical stimulus of analgesia. Complete simultaneous block of all nerves was only obtained in 1 of 16 limbs. CONCLUSION: RUMM block resulted in desensitization of the skin in the associated dermatomes for 4-10 hours. Complete sensory block of the dermatomes supplied by the radial nerve was most consistent. CLINICAL RELEVANCE: RUMM block may be an effective technique to provide adjunctive analgesia for dogs undergoing surgery of the distal aspect of the thoracic limb.

Serotonin and its metabolism in basal deuterostomes: insights from Strongylocentrotus purpuratus and Xenoturbella bocki.

Serotonin (5-HT), an important molecule in metazoans, is involved in a range of biological processes including neurotransmission and neuromodulation. Both its creation and release are tightly regulated, as is its removal. Multiple neurochemical pathways are responsible for the catabolism of 5-HT and are phyla specific; therefore, by elucidating these catabolic pathways we glean greater understanding of the relationships and origins of various transmitter systems. Here, 5-HT catabolic pathways were studied in Strongylocentrotus purpuratus and Xenoturbella bocki, two organisms occupying distinct positions in deuterostomes. The 5-HT-related compounds detected in these organisms were compared with those reported in other phyla. In S. purpuratus, 5-HT-related metabolites include N-acetyl serotonin, gamma-glutamyl-serotonin and 5-hydroxyindole acetic acid; the quantity and type were found to vary based on the specific tissues analyzed. In addition to these compounds, varying levels of tryptamine were also seen. Upon addition of a 5-HT precursor and a monoamine oxidase inhibitor, 5-HT itself was detected. In similar experiments using X. bocki tissues, the 5-HT-related compounds found included 5-HT sulfate, gamma-glutamyl-serotonin and 5-hydroxyindole acetic acid, as well as 5-HT and tryptamine. The sea urchin metabolizes 5-HT in a manner similar to both gastropod mollusks, as evidenced by the detection of gamma-glutamyl-serotonin, and vertebrates, as indicated by the presence of 5-hydroxyindole acetic acid and N-acetyl serotonin. In contrast, 5-HT metabolism in X. bocki appears more similar to common protostome 5-HT catabolic pathways.

Desensitizing the posterior interosseous nerve alters wrist proprioceptive reflexes.

PURPOSE: The presence of wrist proprioceptive reflexes after stimulation of the dorsal scapholunate interosseous ligament has previously been described. Because this ligament is primarily innervated by the posterior interosseous nerve (PIN) we hypothesized altered ligamento-muscular reflex patterns following desensitization of the PIN. METHODS: Eight volunteers (3 women, 5 men; mean age, 26 y; range 21-28 y) participated in the study. In the first study on wrist proprioceptive reflexes (study 1), the scapholunate interosseous ligament was stimulated through a fine-wire electrode with 4 1-ms bipolar pulses at 200 Hz, 30 times consecutively, while EMG activity was recorded from the extensor carpi radialis brevis, extensor carpi ulnaris, flexor carpi radialis, and flexor carpi ulnaris, with the wrist in extension, flexion, radial deviation, and ulnar deviation. After completion of study 1, the PIN was anesthetized in the radial aspect of the fourth extensor compartment using 2-mL lidocaine (10 mg/mL) infiltration anesthesia. Ten minutes after desensitization, the experiment was repeated as in study 1. The average EMG results from the 30 consecutive stimulations were rectified and analyzed using Student's t-test. Statistically significant changes in EMG amplitude were plotted along time lines so that the results of study 1 and 2 could be compared. RESULTS: Dramatic alterations in reflex patterns were observed in wrist flexion, radial deviation, and ulnar deviation following desensitization of the PIN, with an average of 72% reduction in excitatory reactions. In ulnar deviation, the inhibitory reactions of the extensor carpi ulnaris were entirely eliminated. In wrist extension, no differences in the reflex patterns were observed. CONCLUSIONS: Wrist proprioception through the scapholunate ligament in flexion, radial deviation, and ulnar deviation depends on an intact PIN function. The unchanged reflex patterns in wrist extension suggest an alternate proprioceptive pathway for this position. Routine excision of the PIN during wrist surgical procedures should be avoided, as it alters the proprioceptive function of the wrist. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Single stimulation of the posterior cord is superior to dual nerve stimulation in a coracoid block.

BACKGROUND: Both multiple injection and single posterior cord injection techniques are associated with extensive anesthesia of the upper limb after an infraclavicular coracoid block (ICB). The main objective of this study was to directly compare the efficacy of both techniques in terms of the rates of completely anesthetizing cutaneous nerves below the elbow. METHODS: Seventy patients undergoing surgery at or below the elbow were randomly assigned to receive an ICB after the elicitation of either a single radial nerve-type response (Radial group) or of two different main nerve-type responses of the upper limb, except for the radial nerve (Dual group). Forty milliliters of 1.5% mepivacaine was given in a single or a dual dose, according to group assignment. The sensory block was assessed in each of the cutaneous nerves at 10, 20 and 30 min. Block performance times and the rates of complete anesthesia below the elbow were also noted. RESULTS: Higher rates of sensory block of the radial nerve were found in the Radial group at 10, 20 and 30 min (P<0.05). The rates of sensory block of the ulnar nerve at 30 min were 97% and 75% in the Radial and in the Dual groups, respectively (P<0.05). The rate of complete anesthesia below the elbow was also higher in the Radial group at 30 min (P<0.05). CONCLUSIONS: Injection of a local anesthetic after a single stimulation of the radial nerve fibers produced more extensive anesthesia than using a dual stimulation technique under the conditions of our study.

A meta-analysis of studies investigating the effects of lead exposure on nerve conduction.

Group means from nerve conduction studies of persons exposed to lead were used in a meta-analysis. Differences between the control and exposed groups, and the slopes between nerve conduction measurements and log(10) blood lead concentrations were estimated using mixed models. Conduction velocity was reduced in the median, ulnar, and radial nerves in the arm, and in the deep peroneal nerve in the leg. Distal latencies of the median, ulnar, and deep peroneal nerves were longer. No changes in the amplitudes of compound muscle or nerve action potentials were detected. The lowest concentration at which a relationship with blood lead could be detected was 33.0 microg/dl for the nerve conduction velocity of the median sensory nerve. Lead may reduce nerve conduction velocity by acting directly on peripheral nerves or by acting indirectly, for example, on the kidney or liver.

Skin temperature after interscalene brachial plexus blockade.

BACKGROUND AND OBJECTIVES: In neuraxial anesthesia, increase of skin temperature is an early sign of successful block. Yet, during peripheral nerve block of the lower extremity, increase in skin temperature is a highly sensitive, but late sign of a successful block. We hypothesized that after interscalene brachial plexus block, a rise in skin temperature follows impairment of sensation during successful nerve block and occurs only distally, as observed in the lower extremity. METHODS: In the present study, we prospectively evaluated the changes in skin temperature after interscalene brachial plexus blockade in 45 patients scheduled for elective shoulder surgery. We assessed pinprick and cold sensation as well as skin temperature at sites of the skin innervated by the median, ulnar, radial, axillary and musculocutaneous nerve. RESULTS: At the skin areas innervated by the axillary and musculocutaneous nerve, skin temperature did not increase after successful block. At the distal sites, innervated by the median, ulnar, and radial nerve, skin temperature increased significantly (1.9-2.1 degrees C within 30 min) after successful block while it did not after failed nerve block or on the contralateral side. In these areas attenuation of skin sensation preceded a measurable rise in skin temperature (> or =1 degrees C) in 56.3% of nerve blocks, occurred at the same time in 35.2%, and in 8.5% the temperature rise occurred first. CONCLUSIONS: Assessment of skin temperature cannot predict the success of an interscalene brachial plexus block of the axillary and musculocutaneous nerve. Distally, the increase of skin temperature has a high sensitivity and specificity but occurs later than the loss of sensory and motor functions. Therefore, the measurement of skin temperature during interscalene blockade is of limited clinical value.

Spread of injectate associated with radial or median nerve-type motor response during infraclavicular brachial-plexus block: an ultrasound evaluation.

BACKGROUND AND OBJECTIVES: We have compared ultrasound characteristics of spread during infraclavicular brachial-plexus blocks by use of electrically evoked radial-nerve- or median-nerve-type distal motor responses to guide the injection of 30 mL of 1.5% mepivacaine. METHODS: Consecutive patients who required surgery distal to the upper arm were prospectively included in this study. With radial- or median-evoked distal motor response at a stimulating current intensity of less than 0.5 mA, patients were distributed into 2 equal groups. An independent investigator blinded to the evoked response described ultrasound characteristics of the spread of local anesthetic and assessed block quality 30 minutes after placement. A quality diffusion score proportional to the extent and intensity of spread around the axillary artery was used, and dynamic movements during injection were noted. RESULTS: Thirty-two patients were included. With radial-nerve-type motor response, the success rate of infraclavicular plexus block was 100%, but 3 supplemental axillary blocks were requested with median-nerve-type motor response. Quality diffusion scores were significantly higher with radial-nerve-type as compared with median-nerve-type motor response (P = .03). Injection after radial-nerve-type motor response resulted in a typical and reproducible ultrasound feature of posterior local-anesthetic spread associated with medial and upper movement of the axillary artery. With median-nerve-type motor response, failed blocks were associated with a specific posterior displacement of the axillary artery that resulted from superficial spread. CONCLUSION: We have demonstrated that as compared with median-nerve-type motor response, injection performed after a radial-nerve-type motor response promoted reproducible and remarkable ultrasound spread characteristics associated with complete sensory block of the 3 cords at 30 minutes.

A comparison of injection at the ulnar and the radial nerve in axillary block using triple stimulation.

BACKGROUND AND OBJECTIVES: A triple-stimulation technique for axillary block consists of the localization and injection of 2 nerves, median and musculocutaneous, which lie superior to the axillary artery, and of 1 nerve, the radial, which lies inferior. However, in some patients, the ulnar nerve is located first during the search for the radial nerve. The aim of this study was to verify if an ulnar motor response could be considered a satisfactory endpoint as a radial motor response. METHODS: This study was a prospective, randomized, double-blinded study. Ninety patients received a triple-injection axillary brachial plexus block in which the radial nerve (group RAD) or the ulnar nerve (group ULN) was located and injected inferior to the axillary artery. Patients were assessed for sensory and motor block by a blinded investigator at 5-minute intervals over 30 minutes. RESULTS: A statistically significant higher overall block success rate was recorded in group RAD (91% vs. 73%), and this result was related to a larger success rate for anesthetizing the radial nerve (95% vs. 77%). A statistically significant shorter onset time of sensory block for the radial nerve was recorded in group RAD versus group ULN (9 +/- 5 min vs. 16 +/- 7 min), whereas the reverse was true for the ulnar nerve (13 +/- 7 min for group RAD vs. 10 +/- 3 min for group ULN). The time to perform the block was slightly but statistically significantly shorter in group ULN (6.5 +/- 1.7 min vs. 7.8 +/- 1.8 min). CONCLUSIONS: Local anesthetic injection at the ulnar nerve significantly reduces the efficacy and prolongs the onset time of the radial-nerve block when triple-stimulation axillary block is performed.

A comparison of stimulation patterns in axillary block: part 2.

BACKGROUND AND OBJECTIVES: Radial plus musculocutaneous nerve stimulation may have a predominant role in the success of an axillary block, producing more extensive anesthesia of the upper limb than median plus musculocutaneous nerve stimulation. However, no comparison has been made with ulnar plus musculocutaneous nerve stimulation. We compared the extent of both sensory and motor block after ulnar plus musculocutaneous nerve stimulation or radial plus musculocutaneous nerve stimulation. METHODS: Sixty patients were randomly assigned to receive an axillary block using either radial plus musculocutaneous or ulnar plus musculocutaneous nerve stimulation with 40 mL plain 1.5% mepivacaine. Patients were assessed for sensory block by the pinprick method at 5 and 20 minutes. RESULTS: No statistically significant differences were found in the rates of anesthesia at 20 minutes in the cutaneous nerve distributions of the upper limb between radial plus musculocutaneous and ulnar plus musculocutaneous nerve stimulation except for the following nerves: radial (90% and 63.3%, respectively), medial cutaneous of the forearm (83.3% and 100%, respectively), and medial cutaneous of the arm (73.3% and 93.3%, respectively). Global sensory score (minimum: 0; maximum: 12 points) at 20 minutes was significantly higher after radial plus musculocutaneous than after ulnar plus musculocutaneous nerve stimulation: 12 (11-13) and 11 (10-12), respectively. The rates of median nerve blockade were 50% and 53%, respectively. CONCLUSIONS: Radial plus musculocutaneous nerve stimulation produced more extensive anesthesia of the upper limb than did ulnar plus musculocutaneous nerve stimulation. However, there is not an optimal combination of 2 responses in axillary brachial plexus block.

A comparison of proximal and distal radial nerve motor responses in axillary block using triple stimulation.

BACKGROUND AND OBJECTIVES: Stimulation of the radial nerve at the axilla may cause either a proximal movement (forearm extension) or distal movements (supination, wrist or finger extension). In the most recent studies on axillary block, only a distal twitch was accepted as valid. However, this approach was based only on clinical experience. The aim of this study was to verify if a proximal motor response can be considered a satisfactory endpoint. METHODS: This was a prospective, randomized, double-blinded study. One hundred fifty patients received a triple-injection axillary brachial plexus block in which the radial nerve was located by a proximal (group PROX) or a distal motor response (group DIST). Patients were assessed for sensory and motor block of the branches of the radial nerve by a blinded investigator at 5-minute intervals over 30 minutes. RESULTS: An 81% success rate for anesthetizing the sensory distal branches of the radial nerve was seen in group PROX; a significantly higher success rate was recorded in group DIST (95%). The onset time of sensory block for the distal branches of the radial nerve was significantly shorter in group DIST (9.9 +/- 6 v 15.4 +/- 7 minutes). The time to perform the block was slightly shorter and the localization of the nerve simpler in group PROX. The overall block success rate was not significantly different in the 2 groups. CONCLUSIONS: Local anesthetic injection at the proximal radial twitch significantly reduces the efficacy and prolongs the onset time of the radial nerve block. Searching for distal response is significantly more difficult and time consuming than searching for proximal response. However, it does not significantly increase patient discomfort or adverse effects.

The radial nerve should be blocked before the ulnar nerve during a brachial plexus block at the humeral canal.

PURPOSE: The brachial plexus block through the humeral canal as described by Dupré is indicated in hand and forearm surgery. This block requires a multi-stimulation technique that emphasizes the necessity of a rigorous and safe technique. Nerve injury associated with regional anesthesia can entail significant morbidity for patients. Thus, we investigated the brachial block sequence in terms of unintended nerve stimulation as a surrogate of potential nerve injury. METHODS: Sixty patients were randomly allocated in two groups of 30. In Group I the radial nerve was blocked before the ulnar nerve. In Group II the ulnar nerve was blocked before the radial nerve. During the radial nerve approach we recorded, if present, an ulnar nerve response. During the ulnar nerve approach we recorded, if present, a radial nerve response. RESULTS: In Group I while looking for the radial nerve, in 50% of the cases, an ulnar motor response was recorded. In Group II while looking for the ulnar nerve, a radial motor response was recorded in 10% of the cases. CONCLUSION: Our results indicate that the radial nerve should be blocked before the ulnar nerve when performing a brachial plexus block at the humeral canal.