Serotonergic innervation of respiratory motor nuclei after cervical spinal injury: Impact of intermittent hypoxia.

Although cervical spinal cord injury (cSCI) disrupts bulbo-spinal serotonergic projections, partial recovery of spinal serotonergic innervation below the injury site is observed after incomplete cSCI. Since serotonin contributes to functional recovery post-injury, treatments to restore or accelerate serotonergic reinnervation are of considerable interest. Intermittent hypoxia (IH) was reported to increase serotonin innervation near respiratory motor neurons in spinal intact rats, and to improve function after cSCI. Here, we tested the hypotheses that spontaneous serotonergic reinnervation of key respiratory (phrenic and intercostal) motor nuclei: 1) is partially restored 12 weeks post C2 hemisection (C2Hx); 2) is enhanced by IH; and 3) results from sprouting of spared crossed-spinal serotonergic projections below the site of injury. Serotonin was assessed via immunofluorescence in male Sprague Dawley rats with and without C2Hx (12 wks post-injury); individual groups were exposed to 28 days of: 1) normoxia; 2) daily acute IH (dAIH28: 10, 5 min 10.5% O2 episodes per day; 5 min normoxic intervals); 3) mild chronic IH (IH28-5/5: 5 min 10.5% O2 episodes; 5 min intervals; 8 h/day); or 4) moderate chronic IH (IH28-2/2: 2 min 10.5% O2 episodes; 2 min intervals; 8 h/day), simulating IH experienced during moderate sleep apnea. After C2Hx, the number of ipsilateral serotonergic structures was decreased in both motor nuclei, regardless of IH protocol. However, serotonergic structures were larger after C2Hx in both motor nuclei, and total serotonin immunolabeling area was increased in the phrenic motor nucleus but reduced in the intercostal motor nucleus. Both chronic IH protocols increased serotonin structure size and total area in the phrenic motor nuclei of uninjured rats, but had no detectable effects after C2Hx. Although the functional implications of fewer but larger serotonergic structures are unclear, we confirm that serotonergic reinnervation is substantial following injury, but IH does not affect the extent of reinnervation.

Radiological study to evaluate the spreading of two volumes (10 vs. 20ml) of radiological contrast in the block of cutaneous branches of intercostal nerves in medial axillary line (BRILMA) in a porcine experimental model. / Estudio radiológico para evaluar la difusión de dos volúmenes (10 vs. 20ml) de contraste radiopaco en el bloqueo de las ramas cutáneas de los nervios intercostales en la línea medio axilar (BRILMA) en un modelo experimental porcino.

OBJECTIVE: Interfascial blocks of the thoracic wall are being developed as an alternative to central blocks in breast surgery. However, there are few studies that have evaluated the anatomical extension of the local anaesthetic. The objective of this study was to analyse, using fluoroscopy, the spreading of two volumes (10 vs. 20ml) of radiological contrast in the serratus-intercostal plane block in an experimental pig model. MATERIAL AND METHODS: Ten Large-White breed pigs were selected to have a bilateral ultrasound serratus-intercostal plane block performed, with the administering of 10ml and 20ml of iopamidol in the right and left hemithorax, respectively. The spreading of contrast was analysed by fluoroscopy. The Spearman test correlation was used to evaluate the relationship between the administered volume and radiological spreading. A value of P<.05 was considered significant. RESULTS: Twenty anaesthetic blocks were performed, being able to analyse 18 of them. The administration of 10ml of contrast was associated with a mean spreading of 2.28±0.31 (95% CI; 2.01-2.54) intercostal spaces, while the administration of 20ml showed a spreading of 3±0.25 (95% CI; 2.81-3.18) intercostal spaces. There was a significant correlation between the injected volume and the spreading of the contrast (Spearman correlation coefficient of 0.81; P=.0001). CONCLUSION: The results showed a spreading of volume subject to the serratus-intercostal plane block, although not maintaining a 1:1 ratio. Doubling the volume increased the blocked segments by 31%. These findings, if corroborated in the clinical practice, would allow a more precise adjustment in the anaesthetic volume administered.

Local Application of Ultrasound Attenuates Neuropathic Allodynia and Proinflammatory Cytokines in Rats After Thoracotomy.

BACKGROUND AND OBJECTIVES: We aimed to investigate the effect of therapeutic ultrasound (TU) on pain sensitivity and the concentration inflammatory cytokines in a thoracotomy rat model. METHODS: Rats were distributed randomly into 4 groups: (1) sham operated, (2) thoracotomy and rib retraction (TRR), (3) TRR rats that received TU (TRR + TU-1), and (4) TRR rats that received TU with the ultrasound turned off (TRR + TU-0). Ultrasound was set at 1-MHz frequency (1.0-W/cm intensity and 100% duty cycle for 5 minutes), began on postoperative day (POD) 10, and then continued once per day, 5 days a week for 3 weeks. RESULTS: The TRR and TRR + TU-0 rats encountered tactile hypersensitivity from PODs 10 to 28. Mechanical withdrawal thresholds were increased (all P < 0.05) following 5 days of TU, but thresholds remained significantly lower than baseline values. Therapeutic ultrasound increased the subcutaneous, but not body temperature. All groups receiving TRR demonstrated an increase in concentration of interleukin 1ß and tumor necrosis factor α (TNF-α) on POD 14; however, the rise in TNF-α concentration was less in the TU-treated group than in the others. The decrease in concentration was greatest in the TRR + TU-1 group and similar between the TRR and TRR + TU-0 groups. CONCLUSIONS: Mechanical allodynia was partially resolved with TU. Tissue temperature increased with ultrasound, while TU restricted the up-regulation of interleukin 1ß and TNF-α around the injured intercostal nerve.

The Combination of IV and Perineural Dexamethasone Prolongs the Analgesic Duration of Intercostal Nerve Blocks Compared with IV Dexamethasone Alone.

Objective: The use of multiple-level, single-injection intercostal nerve blocks for pain control following video-assisted thorascopic surgery (VATS) is limited by the analgesic duration of local anesthetics. This study examines whether the combination of perineural and intravenous (IV) dexamethasone will prolong the duration of intraoperatively placed intercostal nerve blocks following VATS compared with IV dexamethasone and a perineural saline placebo. Design: Prospective, double-blind, randomized placebo-controlled trial. Setting: Single level-1 academic trauma center. Subjects: Forty patients undergoing a unilateral VATS under the care of a single surgeon. Methods: Patients were randomly assigned to two groups and received an intercostal nerve block containing 1) 0.5% bupivacaine with epinephrine and 1 ml of 0.9% saline or 2) 0.5% bupivacaine with epinephrine and 1 ml of a 4 mg/ml dexamethasone solution. All patients received 8 mg of IV dexamethasone. Results: Group 2 had lower NRS-11 scores at post-operative hours 8 (5.05, SD = 2.13 vs 3.50, SD = 2.50; p = 0.04), 20 (4.30, SD = 2.96 vs 2.26, SD = 2.31; p = 0.02), and 24 (4.53, SD = 1.95 vs 2.26, SD = 2.31; p = 0.02). Equianalgesic opioid requirement was decreased in group 2 at 32 hours (5.78 mg, SD = 5.77 vs 1.67 mg, SD = 3.49; p = 0.02). Group 2 also had greater FEV1 measured at 8, 12, 24, and 44 hours; greater FVC at 24 hours; greater PEF at 28 through 48 hours; and greater FEV1/FVC at 8 and 36 hours. Conclusions: The combination of IV and perineural dexamethasone prolonged the duration of a single-injection bupivacaine intercostal nerve block as measured by NRS-11 compared with IV dexamethasone alone at 24 hours. Reduced NRS-11 at other times, reduced opioid requirements, and increased PFTs were observed in group 2.

Intercostal nerve implants transduced with an adenoviral vector encoding neurotrophin-3 promote regrowth of injured rat corticospinal tract fibers and improve hindlimb function.

Following injury to central nervous tissues, damaged neurons are unable to regenerate their axons spontaneously. Implantation of peripheral nerves into the CNS, however, does result in axonal regeneration into these transplants and is one of the most powerful strategies to promote CNS regeneration. In the present study implantation of peripheral nerve bridges following dorsal hemisection is combined with ex vivo gene transfer with adenoviral vectors encoding neurotrophin-3 (Ad-NT-3) to examine whether this would stimulate regeneration of one of the long descending tracts of the spinal cord, the corticospinal tract (CST), into and beyond the peripheral nerve implant. We chose to use an adenoviral vector encoding NT-3 because CST axons are sensitive to this neurotrophin and Schwann cells in peripheral nerve implants do not express this neurotrophin. At 16 weeks postimplantation of Ad-NT-3-transduced intercostal nerves, approximately three- to fourfold more of the anterogradely traced corticospinal tract fibers had regrown their axons through gray matter below the lesion site when compared to control animals. Regrowth of CST fibers occurred over more than 8 mm distal to the lesion site. No regenerating CST fibers were, however, observed into the transduced peripheral implant. Animals with a peripheral nerve transduced with Ad-NT-3 also exhibited improved function of the hindlimbs when compared to control animals treated with an adenoviral vector encoding LacZ. Thus, transient overexpression of NT-3 in peripheral nerve tissue bridges is apparently sufficient to stimulate regrowth of CST fibers and to promote recovery of hindlimb function, but does not result in regeneration of CST fibers into such transplants. Taken together, combining an established neurotransplantation approach with viral vector-gene transfer promotes the regrowth of injured CST fibers through gray matter and improves the recovery of hindlimb function.

Comparison of plasma lidocaine concentrations after injection of a fixed small volume in the stellate ganglion, the lumbar epidural space, or a single intercostal nerve.

UNLABELLED: We measured the plasma lidocaine concentrations after stellate ganglion block (SGB) and compared them with those after intercostal nerve block (ICNB) and epidural block (EB) using identical doses of lidocaine. Thirty patients undergoing SGB (n = 10), ICNB (n = 10), or EB (n = 10) in our pain clinic participated in this study. Six milliliters of 1% lidocaine was used for all nerve blocks. SGB was performed at the C6 transverse process, ICNB was performed on a single intercostal nerve, and epidural lidocaine was injected through the lumbar epidural catheter. After drug administration, venous blood samples were taken from an indwelling catheter in the arm every minute for the first 10 min and 15, 20, 30, 45, and 60 min thereafter. Plasma lidocaine concentrations were measured by using an enzyme immunoassay method. The SGB group showed significantly higher peak plasma lidocaine concentrations than other groups (SGB 1.65 +/- 0.21 microgram/mL, ICNB 0.89 +/- 0.12 microgram/mL, EB 0.91 +/- 0.19 microgram/mL; P < 0.01). The SGB group reached peak levels significantly faster than the other groups (SGB 3.4 +/- 1.0 min, ICNB 7.9 +/- 1.5 min, EB 6.9 +/- 0.7 min; P < 0.01). We conclude that the plasma lidocaine concentrations after SGB were higher than those after ICNB and EB when using small, equal doses of lidocaine. The high and rapid peak plasma lidocaine concentrations after SGB are probably related to the high vascularity of the injection site. IMPLICATIONS: Higher plasma concentrations of local anesthetics are reportedly obtained after multiple intercostal nerves blocks compared with those after other types of nerve blocks. Our results, however, showed that the peak plasma concentrations after stellate ganglion block were higher and faster than those after a single intercostal nerve block.

Transport of latex microspheres by peripheral nerves of the rat.

The usefulness of rhodamine-labelled latex microspheres (RLM) as a marker for studying intracellular transport in peripheral nerves has been investigated in the intercostal and sciatic nerves of the rat. Suspensions of microspheres were injected into peripheral nerves, and after periods of survival ranging from 24 to 240 h, the nerves and dorsal root ganglia were fixed, frozen sections cut, and sections examined by fluorescence microscopy. It was found that RLM were transported in both anterograde and retrograde directions, but that dorsal root ganglion cells were poorly labelled. Horseradish peroxidase histochemistry did not affect the fluorescence of RLM. Features of the uptake and transport of RLM are discussed and possible applications suggested.

Differentiation of alpha and gamma motoneurons by the retrograde uptake of horseradish peroxidase.

The classification of motoneurons based on size alone may not be an absolute morphological criterion. There appears to be a fair difference in the pattern of horseradish peroxidase uptake between the phrenic and the intercostal motoneurons. Hence we would like to suggest that the gamma and the alpha motoneurons differ in the horseradish peroxidase uptake.