Sciatica is a term used to describe leg pain due to a nerve in the lumbar spine (lower back) being compressed or irritated. The lay public often use the term inaccurately to indicate pain from the back radiating into the leg. The sciatic nerve is a large nerve that serves sensation and motor power to the leg. It takes its nerve supply from a number of nerve roots that exit from the spine at the lower back. The commonest cause is irritation or compression of one of the nerves as it exits the spinal canal. The commonest cause of this is a prolapsed, bulging or even ruptured intervertebral disc pressing on the nerve. The sciatic nerve itself may also be squeezed by spasm of muscles around it in the buttock. This disorder is called Piriformis Syndrome.
The brain is also a major site of apolipoprotein E (apoE) mRNA expression in humans, marmosets, rats and mice.62 Early data from animal lesion paradigms such as sciatic nerve crush 63,64 and entorhinal cortex lesioning 65,66 suggested that apoE plays a role in the coordinated storage and redistribution of cholesterol and phospholipids among cells within the remodeling area. Apolipoprotein E is now believed to play an important role not only in reactive synaptogenesis, by delivering lipids to remodeling and sprouting neurons in response to tissue injury, but also in physiological ongoing synaptic plasticity and maintenance of neuronal integrity, as well as in cholinergic activity. 67-69
In an attempt to improve adrenal graft survival, the sural nerve was cografted with adrenal tissue. The sural nerve is a lower branch of the sciatic nerve, providing sensory information from the leg. Sural nerve cografts introduce a source of nerve growth factor (NGF) from the Schwann cells within the tissue (46-48). Cografts significantly improved chromaffin cell survival (41,49). Furthermore, parkinsonian monkeys with adrenal transplants and sural nerve cografts performed better in skilled reaching tasks than animals with only adrenal grafts (49). Efforts to increase dopamine cell survival are still being investigated. With adrenal medulla grafts, elevating graft survival has been focused more on adding trophic-producing cografts and preventing immunorejection. In fetal mesencephalic tissue transplants, there are many more avenues to investigate to improve dopamine cell survival.
Polyarteritis nodosa in a 47-year-old man. A. The walls of cerebral arteries are grayish and show segmental constriction and distension (string sign). B. A nutrient artery of the sciatic nerve shows acute fibrinoid necrosis with poly-morphonuclear and monocytic leukocytes (HE). Polyarteritis nodosa in a 47-year-old man. A. The walls of cerebral arteries are grayish and show segmental constriction and distension (string sign). B. A nutrient artery of the sciatic nerve shows acute fibrinoid necrosis with poly-morphonuclear and monocytic leukocytes (HE).
Carratu et al.43 showed that low level CO exposures (75 and 150 ppm) to rats from day 0 to day 20 of pregnancy produced modifications of Na+ channel current properties of sciatic nerve fibers of pups. In particular, the inactivation kinetics of transient Na+ current was significantly slowed. The percentage of the maximum number of available Na+ channels at the normal resting potential (-80 mV) was increased to approximately 85 in the CO-exposed pups. The equilibrium potential for Na+ ions also exhibited a negative shift in the CO-treated animals. It appears that mild prenatal exposure to CO produces reversible changes in Na+ channel inactivation kinetics and irreversible changes in Na+ equilibrium potential. These alterations may reflect the role of CO in the development and structural changes of Na+ channels. As voltage-gated Na+ channels are not generally expressed in vascular SMCs or endothelial cells, at least in adult subjects, the likelihood that Na+ channels mediate the...
In a literature review, completed in 1995, of randomized trials of epidural steroid injections in the treatment of low back pain and or sciatica 3 twelve trials were identified, all with flaws in their study design. Six studies showed benefit and six showed either no benefit or worse outcomes after epidural steroid injection. The best quality studies showed inconsistent results and any benefits appeared to be only short term. Therefore the efficacy of epidural steroids was not established. A significant number of side effects and complications, including headache, backache, water retention, fever, bacterial meningitis and epidural abscess, were noted. In 2003 a randomized double blind study concluded that there was no difference between epidural steroid or saline injections for sciatica 4 and in 2005 a review of various treatments 5 concluded that the use of epidural steroid injections could be an effective treatment modality but this statement was qualified noting the lack of current...
The fourth ventricle of adult rats, minced into small fragments, and grafted into the dorsal funiculus at the C2 level in adult rat spinal cord from the same strain (i.e., a syngeneic transplant). At various times posttransplant, subsets of animals were evaluated histologically to confirm cell survival and determine any regenerative effect on the damaged spinal cord. Electron microscopy and fluorescence histochemistry showed that ependymal cells of the grafted CP survived well and induced a robust regeneration of the damaged axons of the spinal cord. Injections of horseradish peroxidase into the sciatic nerve labeled numerous regenerating fibers that extended from the fasciculus gracilis into the graft within 7-d posttransplantation. This effect was evident for at least 10 mo, with some axons elongating rostrally into the dorsal funiculus. Evoked potentials of long duration were recorded 5-mm rostral to the lesion in the rats 8-10 mo after grafting. These findings indicate that CP...
Other systematic reviews have cautioned against over-interpreting findings given the limited number of studies that incorporated rigorous research methodologies. In addition, there is a paucity of prospective studies linking psychological variables to poor outcomes. Recently, Hartvigsen et al. 29 systematically reviewed the literature and identified major methodological problems in the majority of studies. Only 40 prospective studies published between 1990 and 2002 met rigorous scientific criteria. The authors concluded we found moderate evidence for no positive association between perception of work, organization aspects of work, and social support and lower back pain. Therefore, further research that incorporates sound methodologies and prospective studies is needed.
It is also thought that in chronic sciatica, both nociceptive and neuropathic pain components can be distinguished. Neuropathic pain may be secondary to lesions of nociceptive sprouts in the degenerated disc (local neuropathic), mechanical compression of the nerve root (mechanical neuropathic root pain), or secondary to inflammatory mediators (inducing inflammatory neuropathic root pain) all originating from the degenerative disc even without the presence of mechanical compression. Because there can be several different pain mechanisms inducing sciatic pain, it can be called a mixed pain syndrome (126).
Wallerian Degeneration of Nerve Fibers in the CNS Is Accompanied by Increased Expression of Clusterin in Astrocytes and
In situ hybridization with a (32S)-labeled oligonucleotide probe for clusterin mRNA in the L4 spinal cord segment one week following unilateral transection of the sciatic nerve in the adult rat. Note the increased labeling over the ventral and dorsal horns reflecting upregulation in ventral horn motoneurons as well as in astrocytes around the axotomized motoneurons and in the projection territory of the peripherally axotomized primary sensory neurons (right). Bar 500 im. Fig. 8.2. In situ hybridization with a (32S)-labeled oligonucleotide probe for clusterin mRNA in the L4 spinal cord segment one week following unilateral transection of the sciatic nerve in the adult rat. Note the increased labeling over the ventral and dorsal horns reflecting upregulation in ventral horn motoneurons as well as in astrocytes around the axotomized motoneurons and in the projection territory of the peripherally axotomized primary sensory neurons (right). Bar 500 im.
Following peripheral nerve injury, concomitant alternations may be evident in dorsal root ganglia, including transmitter changes and increased density of sympathetic nerve terminals (169). Tyrosine hydroxylase positive cell terminals that produce norepinephrine migrate from vessels supplying the dorsal root ganglion to nerve ganglion cells following sciatic nerve injury. The dorsal root ganglia then express a-adrenergic receptors. This may be a putative link between peripheral tissue injury, nerve injury, and SMP states, such as reflex sympathetic dystrophy and causalgia (complex regional pain syndromes types 1 and 2, respectively). In the periphery, sprouting nerve terminals may exhibit sensitivity to prostaglandins, cytokines, and catecholamines. These kinds of changes further increase the complexity of the neuropathic pain picture and blur the distinctions between nociceptive and neuropathic pain.
Lakhbir Singh and Mark Field performed initial studies of gabapentin for use as an analgesic in animal models in 1992-1993 at the Parke-Davis Cambridge (UK) Research Centre. They found that gabapentin was active in several rat models of antihyperalgesic action (formalin test, carrageenan test),37,38 although at rather high dosages. Gary Bennett obtained a sample of gabapentin in 1993, and tested it in his model of neuropathic pain from sciatic nerve ligation in rats.39 These results from animal models were presented by Bennett at a national meeting in 1994, and at about the same time, the first case reports of gabapentin use for neuropathic pain appeared in the literature.40,41 Subsequently, a large number of investigators found gabapentin to be active in animal models of pain states14,38,42-61 and also in several clinical studies.62-65
The recognition of acupuncture by Western medicine is not entirely new. In the late 1800s, Sir William Osler, one of the most honored and respected physicians and medical educators, wrote a textbook of medicine in which he recommended acupuncture for low back pain and sciatica. In 1901, Gray's Anatomy, a classic medical text, also referred to acupuncture as a treatment for sciatica.
Annexin 1 is up-regulated in multiple sclerosis and in an experimental model of the disease (experimental autoimmune encephalomyelitis-EAE) intracerebroven-tricular administration of annexin 1 proved to be neuroprotective. Annexin 1 is present in both macrophages and astrocytes localised in the lesions (Bolton et al., 1990 Huntinga et al, 1998). In experimental autoimmune neuritis (EAN), a model for human Guillain-Barre syndrome, increased annexin 1 expression was also observed in macrophages and T-cells in the inflamed sciatic nerve (Gold et al.,1999).
Mechanisms involved are poorly understood, which reflects current understanding of neuropathic pain states in general. However, central effects may include alteration in dorsal horn processing and transmission in the tract of Lissauer (240) and suppression of sympathetic outflow from the intermediolateral gray column of the spinal cord. The latter effect may explain improved peripheral blood flow in patients with chronic peripheral vascular insufficiency. The Craig PENS technique, a novel application of electroacupuncture percutaneous neural stimulation (PNS) has been shown effective in herpes zoster, diabetic peripheral neuropathy, and sciatica (241-243).
Corticosteroids are clearly useful for neuropathic pain, particularly in stimulus-evoked pain such as lumbar radiculopathy. The anti-inflammatory effects of corticosteroids are well known, which may partly explain their efficacy for pain. When administered epidurally for treatment of discogenic radiculopathy, corticosteroids inhibit phospholipase A2 activity, and suppress the perineural inflammatory response caused by leakage of disk material around the painful nerve root (314). However, corticosteroids also act as membrane stabilizers by suppressing ectopic neural discharges (231,232). Therefore, some of the pain-relieving action of corticosteroids may be due to a lidocaine-like effect.
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