Analgesic dorsal root ganglion field stimulation blocks both afferent and efferent spontaneous activity in sensory neurons of rats with monosodium iodoacetate-induced osteoarthritis.

OBJECTIVES: Chronic joint pain is common in patients with osteoarthritis (OA). Non-steroidal anti-inflammatory drugs and opioids are used to relieve OA pain, but they are often inadequately effective. Dorsal root ganglion field stimulation (GFS) is a clinically used neuromodulation approach, although it is not commonly employed for patients with OA pain. GFS showed analgesic effectiveness in our previous study using the monosodium iodoacetate (MIA) - induced OA rat pain model. This study was to evaluate the mechanism of GFS analgesia in this model. METHODS: After osteoarthritis was induced by intra-articular injection of MIA, pain behavioral tests were performed. Effects of GFS on the spontaneous activity (SA) were tested with in vivo single-unit recordings from teased fiber saphenous nerve, sural nerve, and dorsal root. RESULTS: Two weeks after intra-articular MIA injection, rats developed pain-like behaviors. In vivo single unit recordings from bundles teased from the saphenous nerve and third lumbar (L3) dorsal root of MIA-OA rats showed a higher incidence of SA than those from saline-injected control rats. GFS at the L3 level blocked L3 dorsal root SA. MIA-OA reduced the punctate mechanical force threshold for inducing AP firing in bundles teased from the L4 dorsal root, which reversed to normal with GFS. After MIA-OA, there was increased retrograde SA (dorsal root reflex), which can be blocked by GFS. CONCLUSIONS: These results indicate that GFS produces analgesia in MIA-OA rats at least in part by producing blockade of afferent inputs, possibly also by blocking efferent activity from the dorsal horn.

Diabetic neuropathy increases stimulation threshold during popliteal sciatic nerve block.

BACKGROUND: Peripheral nerve stimulation is commonly used for nerve localization in regional anaesthesia, but recommended stimulation currents of 0.3-0.5 mA do not reliably produce motor activity in the absence of intraneural needle placement. As this may be particularly true in patients with diabetic neuropathy, we examined the stimulation threshold in patients with and without diabetes. METHODS: Preoperative evaluation included a neurological exam and electroneurography. During ultrasound-guided popliteal sciatic nerve block, we measured the current required to produce motor activity for the tibial and common peroneal nerve in diabetic and non-diabetic patients. Proximity to the nerve was evaluated post-hoc using ultrasound imaging. RESULTS: Average stimulation currents did not differ between diabetic (n=55) and non-diabetic patients (n=52). Although the planned number of patients was not reached, the power goal for the mean stimulation current was met. Subjects with diminished pressure perception showed increased thresholds for the common peroneal nerve (median 1.30 vs. 0.57 mA in subjects with normal perception, P=0.042), as did subjects with decreased pain sensation (1.60 vs. 0.50 mA in subjects with normal sensation, P=0.038). Slowed ulnar nerve conduction velocity predicted elevated mean stimulation current (r=-0.35, P=0.002). Finally, 15 diabetic patients required more than 0.5 mA to evoke a motor response, despite intraneural needle placement (n=4), or required currents ≥2 mA despite needle-nerve contact, vs three such patients (1 intraneural, 2 with ≥2 mA) among non-diabetic patients (P=0.003). CONCLUSIONS: These findings suggest that stimulation thresholds of 0.3-0.5 mA may not reliably determine close needle-nerve contact during popliteal sciatic nerve block, particularly in patients with diabetic neuropathy. CLINICAL TRIAL REGISTRATION: NCT01488474.

Sustained relief of neuropathic pain by AAV-targeted expression of CBD3 peptide in rat dorsal root ganglion.

The Ca(2+) channel-binding domain 3 (CBD3) peptide, derived from the collapsin response mediator protein 2 (CRMP-2), is a recently discovered voltage-gated Ca(2+) channel (VGCC) blocker with a preference for CaV2.2. Rodent administration of CBD3 conjugated to cell penetrating motif TAT (TAT-CBD3) has been shown to reduce pain behavior in inflammatory and neuropathic pain models. However, TAT-CBD3 analgesia has limitations, including short half-life, lack of cellular specificity and undesired potential off-site effects. We hypothesized that these issues could be addressed by expressing CBD3 encoded by high-expression vectors in primary sensory neurons. We constructed an adeno-associated viral (AAV) vector expressing recombinant fluorescent CBD3 peptide and injected it into lumbar dorsal root ganglia (DRGs) of rats before spared nerve injury (SNI). We show that selective expression of enhanced green fluorescent protein (EGFP)-CBD3 in lumbar 4 (L4) and L5 DRG neurons and their axonal projections results in effective attenuation of nerve injury-induced neuropathic pain in the SNI model. We conclude that AAV-encoded CBD3 delivered to peripheral sensory neurons through DRG injection may be a valuable approach for exploring the role of presynaptic VGCCs and long-term modulation of neurotransmission, and may also be considered for development as a gene therapy strategy to treat chronic neuropathic pain.

Differential expression of CaMKII isoforms and overall kinase activity in rat dorsal root ganglia after injury.

Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) decodes neuronal activity by translating cytoplasmic Ca(2+) signals into kinase activity that regulates neuronal functions including excitability, gene expression, and synaptic transmission. Four genes lead to developmental and differential expression of CaMKII isoforms (α, ß, γ, δ). We determined mRNA levels of these isoforms in the dorsal root ganglia (DRG) of adult rats with and without nerve injury in order to determine if differential expression of CaMKII isoforms may contribute to functional differences that follow injury. DRG neurons express mRNA for all four isoforms, and the relative abundance of CaMKII isoforms was γ>α>ß=δ, based on the CT values. Following ligation of the 5th lumbar (L5) spinal nerve (SNL), the ß isoform did not change, but mRNA levels of both the γ and α isoforms were reduced in the directly injured L5 neurons, and the α isoform was reduced in L4 neurons, compared to their contemporary controls. In contrast, expression of the δ isoform mRNA increased in L5 neurons. CaMKII protein decreased following nerve injury in both L4 and L5 populations. Total CaMKII activity measured under saturating Ca(2+)/CaM conditions was decreased in both L4 and L5 populations, while autonomous CaMKII activity determined in the absence of Ca(2+) was selectively reduced in axotomized L5 neurons 21days after injury. Thus, loss of CaMKII signaling in sensory neurons after peripheral nerve injury may contribute to neuronal dysfunction and pain.

Painful neuropathy decreases membrane calcium current in mammalian primary afferent neurons.

Hyperexcitability of the primary afferent neuron leads to neuropathic pain following injury to peripheral axons. Changes in calcium channel function of sensory neurons following injury have not been directly examined at the channel level, even though calcium is a primary second messenger-regulating neuronal function. We compared calcium currents (I(Ca)) in 101 acutely isolated dorsal root ganglion neurons from 31 rats with neuropathic pain following chronic constriction injury (CCI) of the sciatic nerve, to cells from 25 rats with normal sensory function following sham surgery. Cells projecting to the sciatic nerve were identified with a fluorescent label applied at the CCI site. Membrane function was determined using patch-clamp techniques in current clamp mode, and in voltage-clamp mode using solutions and conditions designed to isolate I(Ca). Somata of peripheral sensory neurons from hyperalgesic rats demonstrated decreased I(Ca). Peak calcium channel current density was diminished by injury from 3.06+/-0.30 pS/pF to 2. 22+/-0.26 pS/pF in medium neurons, and from 3.93+/-0.38 pS/pF to 2. 99+/-0.40 pS/pF in large neurons. Under these voltage and pharmacologic conditions, medium-sized neuropathic cells lacked obvious T-type calcium currents which were present in 25% of medium-sized cells from control animals. Altered Ca(2+) signalling in injured sensory neurons may contribute to hyperexcitability leading to neuropathic pain.

Success rates in producing sympathetic blockade by paratracheal injection.

OBJECTIVE: Cervical paratracheal local anesthetic injections (stellate ganglion blocks) are performed to determine the sympathetic contribution to painful and other conditions of the head, neck, and arm. A block is useful for diagnosis only if the desired physiological effect is confirmed, but the frequency with which sympathetic function is successfully blocked is unclear. The goal of this study is to examine the rates of achieving various endpoints of sympathetic interruption by these injections, using commonly available measures of sympathetic change. DESIGN: Retrospective review. SETTING: Training center. PATIENTS: One hundred unselected consecutive blocks in 40 patients. INTERVENTION: Paratracheal sympathetic block at sixth cervical level. OUTCOME MEASURES: Bilateral hand temperature, ophthalmic changes. RESULTS: Horner's syndrome was successfully produced in 84 blocks and the ipsilateral hand warmed by > or = 1.5 degrees C in 60 blocks. However, the contralateral hand also warmed in 31 blocks so that ipsilateral warming exceeded contralateral warming in only 27 blocks, with diminished success by this criterion when the hand was warm before the block. CONCLUSIONS: We conclude that (a) identifying a Horner's syndrome and ipsilateral warming are not by themselves adequate to confirm selective sympathetic blockade; (b) selective sympathetic blockade of the arm is confirmed only if the temperature increase of the blocked side exceeds that of the contralateral side; and (c) cervical paratracheal blocks frequently fail to produce evidence of sympathetic interruption to the arm. Pathophysiological inferences based on these blocks should be made with caution and only with adequate documentation of physiological evidence of sympathetic blockade.

Anatomy of soft tissues of the spinal canal.

BACKGROUND AND OBJECTIVES: Important issues regarding the spread of solutions in the epidural space and the anatomy of the site of action of spinal and epidural injections are unresolved. However, the detailed anatomy of the spinal canal has been incompletely determined. We therefore examined the microscopic anatomy of the spinal canal soft tissues, including relationships to the canal walls. METHODS: Whole mounts were prepared of decalcified vertebral columns with undisturbed contents from three adult humans. Similar material was prepared from a macaque and baboon immediately on death to control for artifact of tissue change after death. Other tissues examined included nerve root and proximal spinal nerve complex and dorsal epidural fat obtained during surgery. Slides were examined by light microscopy at magnifications of 10-40x. RESULTS: There is no fibrous tissue in the epidural space. The epidural fat is composed of uniform cells enclosed in a fine membrane. The dorsal fat is only attached to the canal wall in the dorsal midline and is often tenuously attached to the dura. The dura is joined to the canal wall only ventrally at the discs. Veins are evident predominantly in the ventral epidural space. Nerve roots are composed of multiple fascicles which disperse as they approach the dorsal root ganglion. An envelope of arachnoid encloses the roots near the site of exit from the dura. CONCLUSIONS: These features of the fat explain its semifluid consistency. Lack of substantial attachments to the dura facilitate movement of the dura relative to the canal wall and allow distribution of injected solution. Fibrous barriers are an unlikely explanation for asymmetric epidural anesthesia, but the midline fat could impede solution spread. Details of nerve-root structure and their envelope of pia-arachnoid membrane may be relevant to anesthetic action.

EMLA reduces acute and chronic pain after breast surgery for cancer.

BACKGROUND AND OBJECTIVES: A significant percentage of women undergoing breast surgery for cancer may develop neuropathic pain in the chest, and/or ipsilateral axilla and/or upper medial arm, with impairment in performing daily occupational activities. We designed this study to determine if the perioperative application of EMLA (eutectic mixture of local anesthetics; AstraZeneca) cream in the breast and axilla area reduces analgesic requirements, as well as the acute and chronic pain after breast surgery. METHODS: Forty-six female patients scheduled for breast surgery received randomly 5 g of EMLA or placebo on the sternal area 5 minutes before surgery, and 15 g on the supraclavicular area and axilla at the end of the operation. Treatment with EMLA cream (20 g) or placebo was also applied daily on the 4 days after surgery. In the postanesthesia care unit (PACU), 3, 6, 9, and 24 hours after surgery, and on the second to sixth day postoperatively, pain was assessed by visual analogue scale (VAS) at rest and after movement, and postoperative analgesic requirements were recorded. Three months later, patients were asked if they had pain in the chest wall, axilla and/or medial upper arm, decreased sensation, if they required analgesics at home, and for the intensity of pain. RESULTS: Acute pain at rest and with movement did not differ between the EMLA and control groups, and the analgesics consumed during the first 24 hours were the same for the EMLA and control groups. However, time to the first analgesia requirement was longer (P = .04), and codeine and paracetamol consumption during the second to fifth days was less (P = .001, and P = .004, respectively) in the EMLA versus the control group. Three months postoperatively, pain in the chest wall, axilla, and the total incidence and the intensity of chronic pain were significantly less in the EMLA versus the control group (P = .004, P = .025, P = .002 and P = .003, respectively). The use of analgesics at home and abnormal sensations did not differ between the 2 groups. CONCLUSIONS: The application of EMLA to patients undergoing breast surgery for cancer reduced the postoperative analgesic requirements and the incidence and intensity of chronic pain.

Regional block and mexiletine: the effect on pain after cancer breast surgery.

BACKGROUND AND OBJECTIVES: Breast surgery for cancer is associated with chronic pain and sensory abnormalities. The present study investigates the effect of regional block, oral mexiletine, and the combination of both, on acute and chronic pain associated with cancer breast surgery. METHODS: One hundred patients scheduled for cancer breast surgery received either regional block with 18 mL of 1% ropivacaine intraoperatively and oral mexiletine for the first 6 postoperative days (R + M group), or regional block and placebo (R + PL), or normal saline instead of ropivacaine and mexiletine (PL + M), or normal saline and placebo (PL + PL). Postoperative analgesic requirements were recorded daily. Pain was assessed 0, 3, 6, 9, and 24 hours in the postanesthesia care unit (PACU) and on the second to sixth day postoperatively, at rest, and after movement using the visual analog scale (VAS). Three months after surgery, patients were interviewed for the presence and intensity of pain, abnormal sensations, and analgesic requirements. RESULTS: Regional block reduced the number of intramuscular (IM) injections required the first 24 hours (P =.05), the R + PL group requiring less injections versus the PL + M group (P =.037). Lonarid tablet (paracetamol and codeine) consumption from the second to the fifth postoperative day differed among the 4 groups (P =.0304), the R + M group requiring fewer tablets than the PL + PL group (P =.009). Three hours postoperatively, the R + PL group had less pain at rest when compared with all other groups (P <.05 for all comparisons). On the second postoperative day, VAS at rest and after movement was less in the R + M versus the R + PL group (P <.01 and P <.05, respectively). Three months after surgery, the 4 groups were similar with regard to incidence or intensity of pain or analgesic requirements. The R + PL group had a lower incidence (77%) of reduced or absent sensation (P =.016). CONCLUSIONS: Regional block reduced the analgesic requirements in the early postoperative period, while mexiletine combined with regional block reduced the total analgesic requirements during the next 5 postoperative days. Although chronic pain was not affected by these treatments late-abnormal sensation may be diminished by combination of these treatments. Reg Anesth Pain Med 2001;26:223-228.

Effects of lidocaine and bupivacaine on isolated rabbit mesenteric capacitance veins.

BACKGROUND AND OBJECTIVES: The direct effects of circulating lidocaine and bupivacaine on splanchnic capacitance veins have not been examined previously. This article reports on the effects of clinically relevant concentrations of lidocaine and bupivacaine on adrenergic responsiveness of isolated rabbit mesenteric veins and examines the mechanism of changes. METHODS: Rings of ileal mesenteric capacitance veins were suspended in tissue baths for isometric tension measurements. Effects of lidocaine and bupivacaine on contractile responses to adrenergic nerve stimulation, exogenous norepinephrine (10(-6) M NE), and potassium chloride (80 mM KCl) were examined in endothelium-intact, L-NAME (10(-4) M) treated or denuded veins. RESULTS: Constriction in response to adrenergic nerve stimulation was attenuated by lidocaine and bupivacaine in a dose-dependent manner, with the potency of bupivacaine being higher than lidocaine. Unstimulated or potassium-constricted veins with and without endothelium were unaffected by lidocaine (0.25-100 microg/mL) and bupivacaine (0.1-100 microg/mL). In veins preconstricted by exogenously administered NE, a cumulative increase of both anesthetics produced no effect at low doses, an augmentation of constriction to NE at 5-20 microg/mL bupivacaine and 20-100 microg/mL lidocaine, and minimal effect at 50-100 microg/mL bupivacaine. These actions persisted in denuded or L-NAME treated veins. Nonincremental delivery of high concentrations of lidocaine or bupivacaine produced relaxation of NE and potassium-constricted rings in the absence and presence of L-NAME. CONCLUSIONS: Lidocaine and bupivacaine in concentrations typical during uncomplicated regional anesthesia inhibit adrenergic neurotransmission in rabbit mesenteric capacitance veins and produce modest venodilatation. Higher doses, resembling concentrations during accidental intravascular injection, result in substantial loss in vasomotor control of these capacitance vessels, which may contribute to hemodynamic effects.

Effects of epidural anesthesia on splanchnic capacitance.

Splanchnic veins play an important role in the active control of total body circulatory capacitance. The effects of epidural anesthesia on splanchnic venous capacitance have not previously been examined. A rabbit model using direct measures of mesenteric vein diameter and sympathetic efferent nerve activity was used to test the response to epidural lidocaine at three different doses and to intramuscular lidocaine at two doses. Epidural anesthesia produced hypotension, mesenteric venodilatation, and interruption of sympathetic activity. Maximal changes of these parameters were comparable in the three epidural dosage groups but were more prolonged with increasing dose. High-dose systemic lidocaine caused smaller changes in arterial pressure and sympathetic activity. Further experiments were done to investigate the mechanism of splanchnic venodilatation. Passive vein distension and effects of circulating lidocaine or catecholamines are not likely contributing factors. Blocks limited to thoracic segments, but including the origin of splanchnic preganglionic fibers, produce comparable mesenteric venodilatation and sympathetic interruption as extensive thoracolumbar blocks. Blocks limited to lumbar segments, however, showed mesenteric venoconstriction and increased splanchnic sympathetic activity. The variable responses in splanchnic capacitance with the onset of epidural anesthesia are the result of the competing influences of increased sympathetic activity from decreasing blood pressure and blockade of sympathetic fibers to the splanchnic veins.

Direction and side used to determine the extent of sensory block after subarachnoid anesthesia do not influence the level of the block.

Methods of sensory testing in neuraxial anesthesia may supposedly account for different results in reporting the extent of the block. To determine whether the caudad to cephalad versus the cephalad to caudad direction as well as the side of testing, left versus right, may affect the assessment of sensory block after subarachnoid anesthesia, two groups of patients undergoing transurethral surgery were studied. One group, 44 patients were tested for the influence of direction of block determination and another group 50 patients for the influence of side. Subarachnoid anesthesia was performed with 100 mg of 5% hyperbaric lidocaine using a 25 Whitacre needle with its opening consistently pointing cranially and the patient in the sitting position. To assess the sensory block four lines were drawn bilaterally along the posterior, middle, and anterior axillary lines and a line 5 cm medial to the anterior axillary line. A pressure palpator was moved along each of the four lines and patients were asked to answer if they detected a stimulus, with "yes/no". In the 44 patients assessment of sensory block was performed from caudad to cephalad direction on one side and viceversa on the other. In the other 50 patients the extent of the block was compared between the right and left side. In 44 patients, the level of sensory block determined 20, 25 and 30 minutes after the subarachnoid anesthesia in a cephalad to caudad direction was found at the T11 dermatome at each time point and did not differ when compared to the levels determined following the caudad to cephalad direction. In the second study in a different group of 50 patients, the level of sensory block 20, 25 and 30 minutes after the subarachnoid injection was found at the T11 dermatome on the right side at each time point and did not differ from the level determined on the left side. We conclude that the level of sensory block after subarachnoid anesthesia with lidocaine is independent of the direction of testing and the side the assessment is performed using the pressure palpator.

Neural blockade for upper-extremity pain.

Carefully performed and interpreted neural blockade can be a useful adjunct in both the diagnosis and treatment of painful syndromes of the upper extremity. Pain is a very difficult entity to quantify and diagnose specifically because of its subjective nature, vast differences between patients and their response to pain, and largely because of our inexact understanding of its physiology. Best results of block therapy require thorough understanding of these complexities and limitations, and a rational, careful examination of the data it provides.

Painful nerve injury decreases sarco-endoplasmic reticulum Ca²âº-ATPase activity in axotomized sensory neurons.

The sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) is a critical pathway by which sensory neurons sequester cytosolic Ca(2+) and thereby maintain intracellular Ca(2+) homeostasis. We have previously demonstrated decreased intraluminal endoplasmic reticulum Ca(2+) concentration in traumatized sensory neurons. Here we examine SERCA function in dissociated sensory neurons using Fura-2 fluorometry. Blocking SERCA with thapsigargin (1 µM) increased resting [Ca(2+)](c) and prolonged recovery (τ) from transients induced by neuronal activation (elevated bath K(+)), demonstrating SERCA contributes to control of resting [Ca(2+)](c) and recovery from transient [Ca(2+)](c) elevation. To evaluate SERCA in isolation, plasma membrane Ca(2+) ATPase was blocked with pH 8.8 bath solution and mitochondrial buffering was avoided by keeping transients small (≤ 400 nM). Neurons axotomized by spinal nerve ligation (SNL) showed a slowed rate of transient recovery compared to control neurons, representing diminished SERCA function, whereas neighboring non-axotomized neurons from SNL animals were unaffected. Injury did not affect SERCA function in large neurons. Repeated depolarization prolonged transient recovery, showing that neuronal activation inhibits SERCA function. These findings suggest that injury-induced loss of SERCA function in small sensory neurons may contribute to the generation of pain following peripheral nerve injury.

Subtype-specific reduction of voltage-gated calcium current in medium-sized dorsal root ganglion neurons after painful peripheral nerve injury.

Sensory neurons express a variety of voltage-gated Ca2+ channel subtypes, but reports differ on their proportionate representation, and the effects of painful nerve injury on each subtype are not established. We compared levels of high-voltage activated currents in medium-sized (30-40 µm) dorsal root ganglion neurons dissociated from control animals and those subjected to spinal nerve ligation, using sequential application of semiselective channel blockers (nisoldipine for L-type, SNX-111 or ω-conotoxin GVIA for N-type, agatoxin IVA or ω-conotoxin MVIIC for P/Q-type, and SNX-482 for a component of R-type) during either square wave depolarizations or action potential waveform voltage commands. Using sequential administration of multiple blockers, proportions of total Ca2+ current attributable to different subtypes and the effect of injury depended on the sequence of blocker administration and type of depolarization command. Overall, however, N-type and L-type currents comprised the dominant components of ICa in sensory neurons under control conditions, and these subtypes showed the greatest loss of current following injury (L-type 26-71% loss, N-type 0-51% loss). Further exploration of N-type current identified by its sensitivity to ω-conotoxin GVIA applied alone showed that injury reduced the peak N-type current during step depolarization by 68% and decreased the total charge entry during action potential waveform stimulation by 44%. Isolation of N-type current by blockade of all other subtypes demonstrated a 50% loss with injury, and also revealed an injury-related rightward shift in the activation curve. Non-stationary noise analyses of N-type current in injured neurons revealed unitary channel current and number of channels that were not different from control, which indicates that injury-induced loss of current is due to a decrease in channel open probability. Our findings suggest that diminished Ca2+ influx through N-type and L-type channels may contribute to sensory neuron dysfunction and pain after nerve injury.

ATP-sensitive potassium currents in rat primary afferent neurons: biophysical, pharmacological properties, and alterations by painful nerve injury.

ATP-sensitive potassium (K(ATP)) channels may be linked to mechanisms of pain after nerve injury, but remain under-investigated in primary afferents so far. We therefore characterized these channels in dorsal root ganglion (DRG) neurons, and tested whether they contribute to hyperalgesia after spinal nerve ligation (SNL). We compared K(ATP) channel properties between DRG somata classified by diameter into small or large, and by injury status into neurons from rats that either did or did not become hyperalgesic after SNL, or neurons from control animals. In cell-attached patches, we recorded basal K(ATP) channel opening in all neuronal subpopulations. However, higher open probabilities and longer open times were observed in large compared to small neurons. Following SNL, this channel activity was suppressed only in large neurons from hyperalgesic rats, but not from animals that did not develop hyperalgesia. In contrast, no alterations of channel activity developed in small neurons after axotomy. On the other hand, cell-free recordings showed similar ATP sensitivity, inward rectification and unitary conductance (70-80 pS) between neurons classified by size or injury status. Likewise, pharmacological sensitivity to the K(ATP) channel opener diazoxide, and to the selective blockers glibenclamide and tolbutamide, did not differ between groups. In large neurons, selective inhibition of whole-cell ATP-sensitive potassium channel current (I(K(ATP))) by glibenclamide depolarized resting membrane potential (RMP). The contribution of this current to RMP was also attenuated after painful axotomy. Using specific antibodies, we identified SUR1, SUR2, and Kir6.2 but not Kir6.1 subunits in DRGs. These findings indicate that functional K(ATP) channels are present in normal DRG neurons, wherein they regulate RMP. Alterations of these channels may be involved in the pathogenesis of neuropathic pain following peripheral nerve injury. Their biophysical and pharmacological properties are preserved even after axotomy, suggesting that K(ATP) channels in primary afferents remain available for therapeutic targeting against established neuropathic pain.

A supraomohyoidal plexus block designed to avoid complications.

Interscalene blocks of the brachial plexus are used for surgery of the shoulder and are frequently associated with complications such as temporary phrenic block, Horner syndrome or hematoma. To minimize the risk of these complications, we developed an approach that avoids medially directed needle advancement and favors spread to lateral regions only: the supraomohyoidal block. We tested this procedure in 11 cadavers fixed by Thiel's method. The insertion site is at the lateral margin of the sternocleidomastoid muscle at the level of the cricoid cartilage. The needle is inserted in the axis of the plexus with an angle of approximately 35 degrees to the skin, and advanced in lateral and caudal direction. Distribution of solution was determined in ten cadavers after bilateral injection of colored solution (20 and 30 ml) and followed by dissection. In an eleventh cadaver, computerized tomography and 3D reconstruction after radio contrast injection was performed. In additional five cadavers we performed Winnie's technique with bilateral injection (20 and 30 ml). Concerning the supraomohyoidal block the injection mass reached the infraclavicular region surrounded all trunks of the brachial plexus in the supraclavicular region and the suprascapular nerve in all cases. The solution did not spread medially beyond the lateral margin of the anterior scalene muscle into the scalenovertebral triangle. Therefore, phrenic nerve, stellate ganglion, laryngeal nerve nor the vertebral artery were exposed to the injected solution. Distribution was comparable with the use of 20 and 30 ml of solution. Injections on five cadavers performing the interscalene block of Winnie resulted in an extended spread medially to the anterior scalene muscle. We conclude that our method may be a preferred approach due to its safety, because no structures out of interest were reached. Solution of 20 ml is suggested to be enough for a successful block.

Epidural catheter tip position and distribution of injectate evaluated by computed tomography.

BACKGROUND: The distribution of solutions injected into the epidural space has not been determined. The author therefore examined the site of catheter tips and the spread of contrast material in the epidural space using computed tomographic (CT) imaging in patients receiving successful epidural analgesia. METHODS: Lumbar epidural catheters were placed in 20 female patients by a midline technique. Anesthetic effect was determined by motor and sensory examinations during analgesic infusion. CT images were obtained for identification of the catheter tip and after radiographic contrast injection of 4 ml and then an additional 10 ml. RESULTS: Catheter tips were most often found lateral to the dura in the intervertebral foramen. In these subjects with normally functioning epidural analgesia, there was remarkable interindividual variability in patterns of spread, including various amounts of anterior passage, layering along the dura, and compression of the dura creating a posterior fold. Accumulation becomes more symmetric with increasing injectate volume. Spread through the intervertebral foramina was seen in all subjects. Air and fat in the region of the catheter interfered with solution spread in three subjects, but only over a limited area. Asymmetry in anesthetic effect was attributable to catheter position. No substantial barriers to solution spread were observed. CONCLUSIONS: A variety of catheter tip positions and patterns of solution spread underlie normal epidural anesthesia. Nonuniform distribution of injectate is common and is compatible with uniform anesthesia. Posterior midline structures play a minimal role in impeding distribution of injectate. A far lateral catheter position is a more common cause of asymmetric block than anatomic barriers to solution spread.

Size of human lower thoracic and lumbosacral nerve roots.

BACKGROUND: Nerve root size may determine degree of blockade after epidural or spinal anesthesia, but good measures of this fundamental anatomic parameter have not been published. Models of subarachnoid anesthetic distribution have lacked valid cauda equina dimensions. In this study, the author sought to measure cross-section areas of anterior and posterior roots at different levels for basic anthropomorphic analysis. METHODS: Samples from 12 adult autopsy subjects were obtained from roots at levels T6 through S5. Cross-section area was determined by dividing the root sample weight by length and correcting for tissue density. RESULTS: Roots were variably composed of as many as five easily separable independent strands. Areas of anterior roots are approximately half the area of posterior roots. On average, the largest anterior and posterior root is at S1, but this may occur at L3 through S2. There is a large degree of interindividual variability (e.g., range of posterior L5 root is 2.33-7.71 mm2). CONCLUSIONS: The large size of low lumbar and high sacral roots may cause resistance to anesthetic effects, whereas the smaller dimensions of the thoracic roots may facilitate neural blockade. The small size of the low sacral roots may, in part, explain selective neurotoxic damage of these fibers after subarachnoid injections. Interindividual variability in root sizes may contribute to lack of predictability in anesthetic response.