Sciatica Solution

Sciatica SOS

This ebook teaches you an often-ignored trick that the medical industry refuses to acknowledge to get rid of sciatica pains. This trick comes from the mountains of Nepal; it is natural remedy that gives you all of the pain relief that you need to feel better, just like you deserve. You don't have to succumb to the horrible pains that sciatica will bring you; you can instead feel the relief that comes to people who carefully follow this treatment plan. Your nerves are often too sensitive to put up with much pain or discomfort of any kind; now, you will be able to get rid of that pain and reclaim your manhood; you can do all of the things that you used to be able to do, but now you can do them without fearing that you are going to trigger horrible, debilitating pain in your body! Read more here...

Sciatica SOS Summary

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Author: Glen Johnson
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The writer has done a thorough research even about the obscure and minor details related to the subject area. And also facts weren’t just dumped, but presented in an interesting manner.

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Sciatica and Back Pain Self-Treatment

Sciatica and Back Pain Self- Treatment is a natural way of treating sciatica and back pain problem. It is based on the daily ingestion of special herbal concoction and a completely unique 3-minute routine consisting of 3 easy-to-assume static positions performed in bed or on the floor. During the period of that video, you will simply change your knee positions to influence your back muscles, nerves and spinal discs in a logical progression.The product is a quick fix that has been designed to help you get a cure for your Sciatica and Back Pain in 7 days. The methods employed in this product are natural ones that have been proven by many specialists. The system comes with bonus E-books- The Ultimate Anti-Aging Guide; Smoking Solutions: How to Maintain the Stop Smoking Pledge; Green Smoothie Lifestyle: Drink Your Way to A Slim, Energetic and Youthful Life; The Prevention and Treatment of Headaches.Living without back pain can give you a great day. However, its presence in the body can cause a great level of discomfort and even a lot of unbudgeted expenses. However, when you get a method to relieve this pain, it comes with a great number of benefits.The product is in various digital formats and has been created at a very affordable price. Read more here...

Sciatica and Back Pain SelfTreatment Summary

Contents: Ebooks
Author: John McPherson
Official Website: sciaticahealed.com
Price: $39.00

Disorders of the Back

Of patients with acute low back pain, only 1.5 develop sciatica (i.e., painful paresthesias and or motor weakness in the distribution of a nerve root). However, the lifetime prevalence of sciatica is 40 , and sciatica afflicts 11 of patients with low back pain that lasts for more than two weeks.9,10 Sciatica is associated with long-distance driving, truck driving, cigarette smoking, and repeated lifting in a twisted posture. It is most common in the fourth and fifth decades of life, and peaks in the fourth decade. Most patients with sciatica, even those with significant neurological abnormalities, recover without surgery.11 Only 5 to 10 of patients with persistent sciatica require surgery.5,12 Despite the incidence and prevalence of low back pain and sciatica, the major factor responsible for its societal impact is disability.12 The National Center for Health Statistics estimates that 5.2 million Americans are disabled with low back pain, of whom 2.6 million are permanently...

Expression of some Na channel genes is downregulated in injured neurons

The striking plasticity in Na+ channel expression that can occur in normal neurons raises the question of whether there are alterations in Na+ channel expression in injured neurons. Dorsal root ganglion (DRG) neurons have been especially well studied in this respect. As illustrated in Fig. 5 (middle and bottom rows), following transection of the peripheral axons of DRG neurons (by ligation of the sciatic nerve), expression of mRNA for the SNS (Dib-Hajj et al 1996) and NaN (Dib-Hajj et al 1998a) Na+ channels is down-regulated. The reductions in SNS and NaN transcript expression are paralleled by reduced levels of SNS and NaN Na+ channel protein (Sleeper et al 2000).

Proteins And Proteolytic Enzymes Of Myelin

Acid proteinase activity was demonstrated in CNS samples in the early 1930s and 1940s2728. Subsequently lysosomal proteinases cathepsins A, B, and D were purified from brain samples with increased activities of these proteases observed in diseases29-32. Cathepsin D was found to degrade phenylalanine-phenylalanine linkages in MBP molecules. Acid proteinase activity was also found to be localized in neurons. In contrast to acid proteinases, the demonstration of non-lysosomal neutral proteinase activity in brain was difficult since they are more unstable than lysosomal proteinases. Nonetheless, in the 1950s and 1960s Ansell and Richter33 and Marks and Lajtha34 were able to determine neutral proteinase activity in brain samples35. Since then several neutral proteinases including MPC, calpain, and metalloproteinase activity were found in the brain and later purified 14,20-22,36-43 Aminopeptidases and arylamidases are also found in myelin29,44-47 . In contrast to CNS, the characterization...

The previously silent SNS Na channel gene is abnormally expressed in some demyelinated neurons

FIG. 6. (opposite) In parallel with down-regulation of SNS and NaN channels, slow and persistent TTX-resistant Na+ currents in small DRG neurons are down-regulated following axonal transection within the sciatic nerve. (A) patch clamp recordings showing SNS (left) and NaN (right) currents from representative control DRG neurons. (B) SNS and NaN currents are reduced in axotomized (B, 6 days post-axotomy) DRG neurons. (Modified from Cummins & Waxman 1997.) (C) A rapidly repriming TTX-sensitive Na+ current emerges in DRG neurons following axonal injury. The graph displays the time course for recovery from inactivation at 80 mV for the peak currents, for control (filled circles) and axotomized (open circles, 7 days post-axotomy). Recovery is much faster for the currents in the axotomized neuron. Single exponential functions fitted to the data gave time constants of 160 ms for the control neuron and 41 ms for the axotomized neuron. (D) Time constants for recovery from inactivation for...

Calpain Activation And Inhibition In Demyelinating Diseases

Since increased intracellular calcium levels are required for calpain activation during demyelination, several possible mechanisms have been explored. First, cytosolic calpain may be exposed to calcium levels sufficient for activation as calcium stores (endoplasmic reticulum) are released through the inositol (1,4,5)-triphosphate-mediated pathway as glial inflammatory cells are activated146. Moreover, damaged oligodendrocyte membranes may facilitate calcium influx. In vitro studies have demonstrated vesicular disruption of the myelin sheath, as seen in demyelinating diseases, when rat sciatic nerves were exposed to calcium ionophores at physiological pH147. Previous studies have also shown myelin membranes in rats are susceptible to classical and alternative complement pathways in addition to antibody-dependent complement fixation 148-150. Complement proteins (which enter the CNS as the blood brain barrier is compromised) and perforins have been proposed as possible mechanisms...

Materials and Methods

Table 3.1 Distribution of treated rabbit sciatic nerves Table 3.1 Distribution of treated rabbit sciatic nerves After low-energy SWA (Group I), vacuolic swelling of the axons was visible along the time axis. In some cases the intercellular matrix was assessed as slightly extended (Fig. 3.2). No interruption or clear damage to the sciatic nerve was identified. Walking ability remained unchanged in all animals.

Voltagegated Na channels expressed in small and medium sized sensory neurones

Knowledge of the distribution of Na+ channel a-subunits in the peripheral and centrally projecting axons of rat sensory neurones remains rudimentary. NaV1.6 is the predominant Na+ channel expressed at nodes of Ranvier in myelinated sensory axons 16 . The NaV1.6 subunit is also present throughout the peripheral axon of unmyelinated sensory neurones 17 . Within the rat cornea, NaV1.8 and NaV1.9 are expressed along the entire length of the unmyelinated sensory axons including the nerve terminals in the most superficial layer of the corneal epithelium 18, 19 . Within the sciatic nerve, NaV1.9 is preferentially located in isolectin B4 positive unmyelinated axons and at the nodes of Ranvier of some thinly myelinated axons 19 . In rat DRG, isolectin B4 binds to a subset of nociceptive C neurones 20 . The distribution of NaV1.7 along the axons of sensory neurones has not been reported.

Pathophysiology Of Nucleoside Toxic Neuropathy

Cells were seen in rabbits treated with ddC. It was not possible to determine from the study whether the axonal changes were a primary toxic effect or were secondary to the myelin damage (69). In rats treated with ddI, sections of sciatic nerve taken at various durations after onset of exposure demonstrated myelin toxicity manifested by edema and myelin splitting at 15 wk. Concentrations of ddI used resulted in peak plasma levels five to six times those in humans administered therapeutic doses (70).

LyleJ Micheli MD Christine Curtis BS MEd

Although stress fractures in the lower extremities have been reported extensively 10-12 , stress fractures of the lumbar spine, particularly the pars (spondylolysis), pedicle, and sacrum, also are of concern to the physician. These conditions may manifest as lower back pain, a condition experienced by 35 of adolescent athletes 13 . What is of additional concern is that overuse back injuries are difficult to overcome once they are present and can recur in 26 of males and 33 of females 14 .

Putative role in specific pain syndromes

Nerve injury-induced changes in VGSCs have been well documented in spinal afferents, most notably those comprising the sciatic nerve. While there remains considerable controversy over the relative contribution of specific subpopulations of afferents to the nerve injury-induced changes in nociception (i.e., see 101 ), as well as the relative impact of changes in VGSCs on the excitability of afferents 102 , particularly, small diameter afferents, there is general agreement on a number of key observations. First, nerve injury results in changes in the expression of multiple VGSC a- and P-subunits, including decreases in the expression of NaV1.8 and

Electrodiagnosis Lumbosacral Plexopathies

Several principles of electrodiagnosis in lumbosacral plexopathy are similar to those described in the evaluation of brachial plexus lesions. The anatomy of the lumbosacral plexus is more straightforward again, considering lumbar and sacral plexus separately is helpful. In general, lesions tend to affect either one but rarely both the lumbar and sacral plexus. In cases of lumbar plexopathy, the patient generally presents with quadriceps weakness and the differential diagnostic considerations are femoral neuropathy versus high lumbar radiculopathy (L2-3). The involvement of obturator-innervated muscles localizes a lesion outside of the femoral nerve territory to distinguish lumbosacral plexopathy from radiculopathy, the saphenous SNCS should be performed and paraspinal EMG is important. A patient with a lesion of the sacral plexus will often present with foot drop (inability to dor-siflex the foot) or a flail foot (inability to dorsiflex or plantar flex the foot), and the differential...

Should you arch your back

Neck And Shoulder Muscles

* For people suffering from congenital spondylolysis (incomplete fusing of the vertebral arch), putting the lumbar spine in extension can cause the vertebra to slide (spondylolisthesis), which may cause serious nerve compression and lead to sciatica. * For people who are not fully grown or people experiencing osteoporosis, extending the lumbar spine may lead to spondylolysis because of fractures in the vertebral arch. This fracture in the posterior anchoring system of the vertebra may allow the vertebra to slide forward and seriously compress the neural elements (which leads to sciatica). With spondylolysis (fracture of the vertebral arch) the vertebra may slide forward (spondylolisthesis) and compress the neural elements, causing sciatica. With spondylolysis (fracture of the vertebral arch) the vertebra may slide forward (spondylolisthesis) and compress the neural elements, causing sciatica.

Specific Disorders Of The Brachial Plexus

Lumbosacral Plexus Schematic

The sacral plexus derives from L4 through S4 nerve roots and gives rise to the largest nerve of the plexus, the sciatic nerve. The sciatic nerve supplies the hamstring muscles and all the muscles below the knee through its two branches the peroneal and tibial nerves. The superior and inferior gluteal nerves arise from the sacral plexus proximal to the sciatic nerve and supply the gluteus muscles.

Lower Motor Neuron Pool

The lumbosacral plexus is derived from the anterior primary rami of the twelfth thoracic through the fourth sacral levels and is contained within the psoas major muscle. Although many more roots contribute to the lumbosacral plexus, it is somewhat simpler than the brachial plexus. Two major nerves, the femoral nerve and the sciatic nerve, are formed from the plexus (see Fig 15-7 ).

Lower Motor Neuron Syndromes

It is less likely to be injured by trauma than the brachial plexus, but pelvic hematomas in the psoas muscle resulting from anticoagulation and surgical trauma are more common. Lesions of the lumbar segments produce weakness of all movements of the thigh with reduction or loss of the patellar tendon jerk. Lesions of the sacral portion of the plexus result in a weakness of the foot and flexion of the knee with reduction or loss of the ankle jerk. Because most of the motor output of the lumbar portion of the plexus is contained in the femoral nerve and the output of the sacral portion is found in the sciatic nerve, it may be difficult to distinguish lumbosacral plexus lesions from lesions of their respective major peripheral nerves. To distinguish a lumbar plexus lesion from a femoral neuropathy, a diligent search should be made for weakness of the adductor muscles innervated by the obturator nerve or of sensory loss in the inguinal region or over the...

Neuromodulatory drugs

The concept of pharmacologic neuromodulation refers to the idea that patients could use pharma-cologic agents that can either protect nerves from trauma or enhance nerve regeneration following injury. There is excellent animal data supporting this concept in facial, tibial, and sciatic nerve injury models. The most widely-studied group of compounds are immunophilin ligands. Immunophilins are found in immune tissue, but are in the range of 50-100-fold greater concentrations in neural tissue,

Sacral Stress Fractures

There are two types of sacral stress fractures insufficiency fractures and fatigue fractures. Insufficiency fractures are more common and usually occur in osteo-porotic bone, with minimal or unremembered trauma 78,79 . Thus, this type occurs more commonly in elderly females and are frequently bilateral, presenting as lower back pain 78 . In the athletic population, sacral stress fractures (considered fatigue fractures resulting from their mechanical cause) are an uncommon cause of lower back pain 6 . The prevalence is unknown 6 however, studies have shown that they appear to be more common in female athletes 27,28,80 . They have been reported in such athletes as distance runners and volleyball players (Fig. 5) 24,25,71,72,74 . In patients presenting with lower back pain, differential diagnoses include degenerative disk disease and sacroiliac joint dysfunction 6,24,27 .

Sodium channel expression in DRG neurons during neuroma formation

Transection of peripheral nerve leads to formation of a neuroma, which in its distal 1,000 im is characterized by a tangle of axonal endbulbs and sprouts, de- and dys-myelinated axons, and extensive disorganized connective tissue 34 , and is accompanied by the development of abnormal spontaneous activity (ectopic discharge) in many primary sensory neurons 35, 36 . The aberrant electrical activity can arise at the site of injury 20, 37, 38 or within the DRG cell body 7, 22, 39 . Early studies demonstrated accumulations of sodium channels at the distal tips of transected axons 40-42 . More recent work has identified specific sodium channel isoforms that accumulate within neuromas 43, 44 and that may contribute to hyperex-citability in this region. Transection of the sciatic nerve is also accompanied by alterations in the expression of several sodium channel isotypes in the cell bodies of DRG neurons 33, 45, 46 . Three sodium channel isoforms - NaV1.3, NaV1.8 and NaV1.9 - markedly change...

Specialisations At Nodes Of Ranvier

Rat Sciatic And Neuroma

Figure 3.5 N-syndecan in Schwann cell microvilli. These are images of paraformaldehyde fixed fibres from adult rat sciatic nerve, immunostained for N-syndecan (red), Na+ channels (green), and neurofilament-heavy NF-H (blue). N-syndecan is localised to Schwann cell microvilli situated around the node while Na+ channels localise to the node on the axolemma. Note that in cross-section Na+ channels lie inside N-syndecan staining (inset). Scale bar 5 mm. A colour version of this Figure is in the Plate section. Figure 3.5 N-syndecan in Schwann cell microvilli. These are images of paraformaldehyde fixed fibres from adult rat sciatic nerve, immunostained for N-syndecan (red), Na+ channels (green), and neurofilament-heavy NF-H (blue). N-syndecan is localised to Schwann cell microvilli situated around the node while Na+ channels localise to the node on the axolemma. Note that in cross-section Na+ channels lie inside N-syndecan staining (inset). Scale bar 5 mm. A colour version of this Figure is...

Proteases In Demyelination In Vitro

But the co-operative action of phospholipases and proteolytic enzymes, e.g. trypsin, results in a more extensive loss of the basic protein and proteolipid protein and conversion of myelin phosphoglycerides to the corresponding lysocompounds 1 6. When injected under the perineurium of the sciatic nerve, both trypsin and phospholipase produce lesions in the myelin sheath, with lamellar splitting and expansion of the myelin structure as observed in electron micrographs. The product of lecithin hydrolysis, lysolecithin, has been demonstrated to produce extensive demyelination both in vivo and in vitro17. Not all myelin proteins are equally vulnerable to proteolysis and these will be individually addressed, initially in in vitro systems.

Differentiation Studies

NERVOUS SYSTEM MSCs have been tested as therapeutic agents for the repair of brain injury. Mice injected with bromodeoxyuridine-tagged MSCs were shown to express NruN, a neuronal-specific protein and glial fibrillary acidic protein, and functional tests indicated significant recovery from cerebral artery occlusion as compared to vehicle-only controls (Li et al., 2000). In a drug-induced model of Parkinson's disease, mice injected with MSCs expressed tyrosine hydroxylase and exhibited significant improvement in functional testing (Li et al., 2001b), and in a model for stroke, MSC-injected rats showed improvement in neurological severity scores (Li et al., 2001a). MSCs have also been shown to promote peripheral nerve repair. Rat MSCs cultured in the presence of forskolin, basic fibroblast growth factor, platelet-derived growth factor, and heregulin were transplanted into the cut ends of sciatic nerves and were able to differentiate into cells expressing myelinating proteins...

MSCs Applied to Small Animal Models

Another class of cells, the muscle-derived stem cells, has also been evaluated for their potential in repairing bone defects. Many reports have suggested that within skeletal muscle there are inducible osteoprogenitor cells that can be stimulated to produce bone. The previously described report by Urist demonstrated that implanted cancellous bone can induce ectopic bone in skeletal muscle (96). Khouri et al. evaluated the ability of BMP-3 to induce bone in a variety of body tissues, including Achilles tendon, adductor muscle, epididymal fat, kidney, liver, sciatic nerve, and spleen (123). BMP-3 induced the most bone when injected into skeletal muscle. The bone regenerative capabilities were further evaluated by implanting a muscle flap injected with BMP-3 protein into a calvarial defect. With this implant, the calvarial defect was completely healed. This pioneering study laid the foundation for future investigations evaluating skeletal muscle and muscle-derived stem cells for bone...

Sodium channel expression in spinal cord dorsal horn neurons following peripheral nerve injury

Pgp9 Expression Dorsal Horn

Chronic constriction injury (CCI) of sciatic nerve upregulates Nay1.3 and downregulates Nay1.8 and Nay1.9 in DRG neurons. A. Quantification of RT-PCR products from control (C) and CCI DRG 14 days post surgery demonstrates a significant downregulation of Nay1.8 and NaV1.9 mRNA (NaV1.8 512 bp NaV1.9 392 bp). NaV1.3 transcripts are upregulated in CCI neurons (Nav1.3 412 bp). B. In situ hybridization of small neurons from control and CCI DRG shows that hybridization signals for Nav1.8 and Nav1.9 are significantly reduced in CCI Chronic constriction injury (CCI) of sciatic nerve upregulates Nay1.3 and downregulates Nay1.8 and Nay1.9 in DRG neurons. A. Quantification of RT-PCR products from control (C) and CCI DRG 14 days post surgery demonstrates a significant downregulation of Nay1.8 and NaV1.9 mRNA (NaV1.8 512 bp NaV1.9 392 bp). NaV1.3 transcripts are upregulated in CCI neurons (Nav1.3 412 bp). B. In situ hybridization of small neurons from control and CCI DRG shows that hybridization...

Discussion

Schelling et al. (1994) removed sciatic nerves of frogs and exposed the nerves to shock waves in an organ bath. The nerves were mounted in a chamber which allowed electrical nerve stimulation and the registration of electrically and shock wave-induced compound action potentials. Action potentials were regularly evoked by SWA. If the focus of the shock wave was placed outside of the nerve, electrical response declined dramatically. The current animal study revealed no significant changes of the rabbit sciatic nerve in the sense of an axonotmesis or neurotmesis. However, there were clear signs of a histologi-cally visible reaction of the nerve fibers and the adjacent perineurium, particularly after high-energy SWA.

Conclusions

It was proposed that Na+ channel b2 subunits, because of their homology to F3 contactin, may interact in a lateral or cis fashion with NrCAM and thus contribute to Na + channel localization. Our data expand this model to propose a direct link between Na+ channels and ankyrinG through homophilic b subunit interactions (Malhotra et al 2000) (Fig. 1). The multivalent membrane binding domain of ankyrinG (Michaely & Bennett 1993) may allow interaction with multiple CAMs, including neurofascin, NrCAM, as well as Na + channel b subunits, forming a Na+ channel signalling complex at the node of Ranvier that may also include contactin (Kazarinova-Noyes et al 2001). b subunit mRNA expression has been described in sciatic nerve Schwann cells, astrocytes from spinal cord, optic nerve and sciatic nerve, and B104 oligodendrocyte precursor cells in culture (Dib-Hajj et al 1996, Oh et al 1997, Oh & Waxman

Humoral Responses

Figure 10.8 Electron micrograph from sciatic nerve of rabbit with CREAN. Peroxidase-conjugated anti-IgG labels galactocerebroside antibodies found on Schwann cell plasmalemma of both myelinated (a) and unmyelinated (b) fibres. Figure 10.8 Electron micrograph from sciatic nerve of rabbit with CREAN. Peroxidase-conjugated anti-IgG labels galactocerebroside antibodies found on Schwann cell plasmalemma of both myelinated (a) and unmyelinated (b) fibres.

Peroneal Neuropathy

The peroneal nerve fibers are derived from the L4-S1 nerve roots. These fibers travel through the lumbosacral plexus, and continue on through the sciatic nerve. Within the sciatic nerve, fibers of the common peroneal nerve run separately from tibial nerve fibers. The common peroneal nerve first gives off the lateral cutaneous nerve of the calf. Near the fibular neck, the common peroneal nerve divides into its terminal branches, the superficial and deep peroneal nerves.

Spondylolysis

Spina Bifida Occulta Pain

Spondylolysis, a stress fracture of the pars interarticularis (the part of the lamina located between the superior and inferior articular processes of the vertebrae), is one of the most common conditions associated with lower back pain in adolescent athletes 35 . In the adolescent athlete population, the fracture of the pars interarticularis occurs at a time of spinal growth in the posterior elements, as well as anterior elements of the attached growth plate 36 . A recent study at Children's Hospital Boston 37 examined 100 athletic patients under the age of 18 who had back pain and found spondylolysis present in 47 of these patients. Spondylolysis caused by overuse injuries is increasingly being diagnosed in younger patients between 5 and 10 years of age 7,37-39 . These findings demonstrate the high occurrence of spondylolysis in the adolescent athletic population and the increasing importance of physician vigilance in its early detection. Spondylolysis in the athletic population is...

Conclusion

Weakness of knee flexion is a sciatic nerve mediated movement. Likewise, weakness of hip adduction, although also suggesting involvement of the L2-L4 nerve roots, is mediated by the obturator nerve. Hip flexion is mediated by the iliopsoas muscle group however, this muscle group arises proximal to the inguinal ligament and would be expected to be spared. The medial and intermediate cutaneous nerve of the thigh and the saphenous nerves, all of which arise from the femoral nerve and would be affected in compression at the level of the inguinal ligament, mediate sensory disturbance over the anterior and medial aspect of the distal thigh as well as the medial calf. Weight gain, preexisting obesity, pregnancy, and the wearing of tight work belts may predispose to this type of injury.

Sciatic Neuropathy

The sciatic nerve derives its supply from the L4-S2 nerve roots. The nerve arises from the lumbosacral plexus, and exits the pelvis through the greater sciatic foramen before traveling under the piriformis muscle. The nerve itself consists of two distinct trunks, the lateral trunk (peroneal) and medial trunk (tibial). Branches originating in the proximal thigh arise predominantly from the tibial division. The tibial division supplies the hamstring muscles, with the exception of the short head of the biceps femoris, which receives its supply from the peroneal division. All muscles below the knee receive innervation from the sciatic nerve through one of its two divisions (peroneal or tibial). Afferent sensory input from the leg also travels in the sciatic nerve, except for that region supplied by the saphenous nerve. 7.2. Clinical Features of Sciatic Nerve Dysfunction

Acupuncture

The rate of lumbar surgery in the United States is 40 higher than in most developed nations, and five times higher than in England and Scotland.53 The lifetime prevalence of lumbar spine surgery ranges between 1 and 3 , and 2 to 3 of patients with low back pain may be surgical candidates on the basis of sciatica alone.12 Surgery rates vary widely by geographical region in the United States and have risen dramatically in the last ten years.54 Psychological factors influence postsurgical outcomes more strongly than initial physical examination or surgical findings. Prior to surgery, patients should be evaluated with standard pain indices, activities of daily living scales, and psychometric testing. Surgical results for treating symptomatic lumbar disc herniation unresponsive to conservative therapy are excellent in well-selected patients.55 Indications. There is no evidence from clinical trials or cohort studies that surgery is effective for patients who have low back pain...

NaV18 in nociceptors

Table 1 summarises the NaV1.8 expression in various models of neuropathic pain. Ligation of L5 and L6 spinal nerves (spinal nerve ligation model, SNL) leads to a reduction in the levels of NaV1.8 mRNA and protein in the cell bodies of these neurons concomitant with a reduction in the TTX-r current in these neurons 36, 37 . There is a large increase in NaV1.8 immunoreactivity in the sciatic nerve after L5 L6 ligation which is attributed to redistribution of NaV1.8 from the cell bodies of the L4 DRG (which are still intact) to the sciatic nerve 37 . Concomitant with the increased levels of NaV1.8 in the injured axon, C-fibre conduction in these nerves is much more resistant to TTX than in control nerves, implying that after nerve damage more of the afferent activity is dependent on NaV1.8 37 . Application of NaV1.8 antisense oligonucleotides intrathecally prevents the upregulation of NaV1.8 in the sciatic nerve and eliminates the TTX-r component of the C-fibre conduction. The effect of...

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