|Sciatica: Studies of symptoms, genetic factors, and treatment with periradicular infiltration|
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Data on the determinants are largely based on cross-sectional studies, although longitudinal cohort studies potentially yield more relevant information. In the following chapters, determinants of lumbar disc disease (herniated disc or typical sciatica) are reviewed in three parts: constitutional factors such as body height, age, gender and obesity; environmental and behavioural factors such as occupation, smoking, leisure time activities and psychological factors; and finally genetic factors, knowledge of which is increasing constantly.
Sciatica and risk of undergoing surgery is highest during the fourth and fifth decades of life (Kelsey & Ostfeld 1975, Frymoyer 1988). This age-related vulnerability is also supported by findings from cadaver studies (Adams & Hutton 1982), and it may be related to greater prevalence of disc ruptures. The reduced incidence of disc herniation in old persons may be related to the loss of turgor and elasticity of discs with age.
Male predominance of HNP has been observed among patients hospitalized for sciatica (Spangfort 1972, Naylor 1974, Thomas et al. 1983). On the other hand, in one study prevalence of sciatic symptoms did not differ between males and females (Kelsey & Ostfeld 1975). In the mid-1980s the prevalence of lumbar disc syndrome in Finland was 5.1% for men and 3.7% for women aged 30 years or over (Heliövaara et al. 1987a). The diagnosis was based on medical history, symptoms and physical examination. In a recent longitudinal Finnish cohort study, the incidence of disc disease (HNP or sciatica) at the age of 28 was 12.8 per 1000 for men and 6.6 per 1000 for women (Zitting et al. 1998), concordant with the earlier observations of male predominance.
Body height seems to predispose to sciatica (Hrubec & Nashold 1975, Weir 1979, Merriam et al. 1983), although in some studies no association was found (Kelsey & Ostfeld 1975, Kelsey et al. 1984). In a Finnish survey, body height was a significant risk factor for HNP in both sexes (Heliövaara 1987a). The relative risk increased on average by 5 % among men and 4 % among women per one centimetre increase in body height. The risk was evident above heights of 180 cm for men and 170 cm for women (Heliövaara 1987a).
Obesity measured as body mass index has been found to be a significant predictor of disc disease only in men (Heliövaara 1987a). Herniations are often found in asymptomatic subjects (Boden et al. 1990, Jensen et al. 1994), but narrowing of the lumbar canal may predispose to symtomatic disc lesions and sciatica as the space is limited (Porter et al. 1978, Heliövaara et al. 1986).
Heavy physical loading and materials handling, including lifting, bending, twisting, sitting and sustained nonneutral postures predispose to low back pain (Magora 1973). Similarly, hard physical jobs and, in particular, frequent lifting and postural stress are known to increase the risk of sciatica (Heliövaara 1989, Riihimäki et al. 1989). Motor vehicle driving is also positively associated with HNP and sciatica (Kelsey & Hardy 1975, Kelsey et al. 1984, Heliövaara 1987b). The incidence of sciatica during a 3-year follow-up period was 22% for machine operators, 24% for carpenters and 14% for office workers (Riihimäki et al. 1994). However, lifetime loading is more relevant than current conditions (Videman & Battie 1999). Moreover, many occupations are also associated with various lifestyle factors that can act as confounding factors in attempts to determine occupational effects (Ilmarinen et al. 1991). When lumbar disc degeneration among Finnish twins was studied, heavier lifetime occupational and leisure physical loading was associated with greater disc degeneration at the upper lumbar levels, whereas sedentary work was associated with lesser degeneration (Battie et al. 1995).
Accident-related trauma has also been suspected of causing structural damage and accelerating degenerative changes (Videman et al. 1990). The risk of sciatic pain has indeed been reported to be increased among workers who had earlier had back accidents (Riihimäki 1985, Riihimäki et al. 1989, Heliövaara et al. 1991).
Self-assessed stenuousness of work was a significant risk factor for sciatica in women (Heliövaara 1987b). In a Finnish follow-up study, distress symptoms predicted hospital admissions for HNP or sciatica among women who reported no severe back trouble at entry (Heliövaara et al. 1987b, Heliövaara et al. 1991). The findings are in agreement with a recent experimental study where the influence of psychosocial stress, gender and personality on mechanical loading of the lumbar spine was evaluated (Marras et al. 2000). Psychosocial stress increased spine compression and lateral shear on the basis of differences in muscle coactivation. Women"s anterior-posterior shear forces increased in response to stress, whereas men"s decreased. Certain personality traits (e.g. introverts and thinkers) were associated with increased spine loading compared with those with an opposing personality trait, and explained loading differences between subjects (Marras et al. 2000).
The effect of smoking on the incidence of sciatica is controversial. In a Finnish follow-up study, smokers and ex-smokers had a similar increased risk of sciatica (Manninen et al. 1995), whereas in other studies smoking was of borderline or no significance (Heliövaara et al. 1987b, Riihimäki et al. 1994).
Findings of a study with Finnish identical twin pairs indicated that environmental factors account for more than 80 % of the aetiology of sciatica, whereas genetic factors were more significant in individuals under 40 years (Heikkilä et al. 1989). In the same study population, determinants of lumbar disc degeneration were also studied (Battie et al. 1995). In multivariate analyses, the mean job code and age together explained only 16 % of the variability in degeneration at the upper levels, whereas addition of familial aggregation improved the model so that 77 % of the variability was explained (Battie et al. 1995). At the lower levels, the model explained only 43 % of the variability, but here also familial aggregation, including both genetic influences and early childhood environment, was the most important determinant. In concordance with the twin studies, several authors have reported the association of a positive family history of low back pain, sciatica or herniated disc in adolescents with herniated discs (Nelson et al. 1972, Zamani & MacEwen 1982, Gunzburg et al. 1990, Varlotta et al. 1991). When adolescent patients with disc herniation were compared with matched controls, 32% of patients had first-degree relatives with a history of severe back pain, sciatica or herniated disc compared with 7% in the control group (Varlotta et al. 1991). It was estimated that the risk of developing a herniated lumbar disc before the age of 21 years was four to five times greater in adolescents with a positive family history.
The search for candidate genes is ongoing. Recently, two intragenic polymorphisms of the vitamin D receptor gene revealed an association with disc degeneration and anular tears (Videman et al. 1998, Videman et al. 2001). However, the role of vitamin D receptor gene polymorphism in disc disease is somewhat unclear because the receptor is not found in the discs. Aggrecan, on the other hand, is a major constituent of the disc. The coding region of the aggrecan gene contains a highly conserved repeat region. A total of 13 alleles differing by the number of nucleotide repeats have so far been observed. As the result of this polymorphism, aggrecan core proteins of different lengths are expressed. Multilevel and severe disc degeneration was found to be present in the individuals with a shorter tandem repeat length of aggrecan gene (Kawaguchi et al. 1999). In mice, homozygotes for a deletion mutation of aggrecan died shortly after birth because of respiratory failure (Watanabe et al. 1997). The phenotype of heterozygotes included slight dwarfism and a delayed onset spinal disorder. Within 19 months of age, the mice exhibited spastic gait due to misalignment of cervical spine. Histological examination revealed a high incidence of disc herniations and disc degeneration (Watanabe et al. 1997).
Collagen IX is a heterotrimeric protein consisting of three genetically distinct α chains, α1(IX), α2(IX) and α3(IX), encoded by the COL9A1, COL9A2 and COL9A3 genes (Shaw & Olsen 1991, Brewton & Mayne 1994, Pihlajamaa et al. 1999, Paassilta et al. 1999). Collagen IX is covalently cross-linked to the surface of the collagen II fibril, and a portion of the molecule projects away from the fibril surface (Wu & Eyre 1989, Brewton & Mayne 1994). Collagen IX is believed to function as a bridge between collagen fibril structure and other matrix molecules (Figure 2). Its role in intervertebral disc disease is supported by the findings of transgenic mice expressing mutant α1(IX) chain (Kimura et al. 1996). These mice developed accelerated intervertebral disc degeneration with partial disruption of endplates and fissures in the anulus. A sequence variation in the COL9A2 gene that changes a codon for glutamine to one for tryptophan in the α2 chain of collagen IX (Trp2 allele) has been found to associate with dominantly inherited disc disease characterized by sciatica in about 4 % of Finnish patients (Annunen et al. 1999). This allele was not detected in the controls. Recently, a similar sequence variation changing a codon for arginine to one for tryptophan was found in the COL9A3 gene coding for the α3 chain of collagen IX (Trp3 allele) (Paassilta et al. 2001). The Trp3 allele was observed in 24.4% of the sciatic patients, but in only 9.3% of the controls. The allele was found to increase the risk of lumbar disc disease almost threefold, representing the first common genetic risk factor for the disease (Paassilta et al. 2001). Since tryptophan is not normally found in collagen IX it is possible that, as the most hydrophobic amino acid, it may render intervertebral discs fragile by disturbing the collagen triple helix or interfering with the molecular interactions (Annunen et al. 1999, Paassilta et al. 2001).
Figure 2. A schematic presentation of collagen IX. It is covalently cross-linked to the surface of collagen II fibril, but a portion of the molecule projects from the fibril surface. Collagen IX is a heterotrimeric protein consisting of three genetically distinct a chains, α1(IX), α2(IX) and α3(IX). Helical domains are interrupted with globular domains (circles). The glycosaminoglycan (GAG) chain is attached to an α3-chain. The defect in α2(IX) leads to a change of codon for glutamine to that for tryptophan, which may interrupt the covalent binding of collagen IX with collagen II.