Sciatic neurectomy in CIA rats

Fig. 3. Lateral hind paw radiographs of a rat of the CIAgroup (A) and another of the CIA + NTx group (B) at 6weeks after the initial sensitization. Proliferation of radioresistant tissue and bone destruction in the ankle andsubtalar joints (arrows) is less prominent in the CIA+NTx group than the CIA group. CIA, collagen sensitization; NTx, sciatic neurectomy.

Fig. 4. Changes in total BMD (A), cancellous BMD (B)and cortical BMD (C) of tibial metaphysis. aP < 0.05
and bP < 0.01 compared with sham rats (Dunnett’s test).
eP < 0.05 compared with CIA rats (Dunn’s test). Values
expressed as mean ± SE. BMD, bone mineral density;
CIA, collagen sensitization; NTx, sciatic neurectomy.

BMD was significantly lower in the CIA, NTx
and CIA + NTx groups than in the sham groupat 4 and 8 weeks after the initial sensitization,
but there was no signiﬁcant difference among theNTx, CIA + NTx and CIA groups (Fig. 4B). The
cortical BMD gradually increased in the shamgroup but gradually decreased in the NTx andCIA + NTx groups. It was signiﬁcantly lower inthe NTx and CIA + NTx groups than in the shamgroup at 4 and 8 weeks, and in the CIA+NTx
group than in the CIA group at 4 weeks after theinitial sensitization (Fig. 4C).

Discussion
Several studies have been reported on arthritis
and periarticular bone loss in animal models ofRA (Hanyu et al., 1999; Enokida et al., 2001;
Hoshino et al., 2001; Yamasaki et al., 2001), but
few on arthritis and paralysis. It has been shownthat sciatic neurectomy causes bone loss in thelower limbs of the animal models (Okumura etal., 1987; Murakami et al., 1994; Iwamoto et al.,61

M. Kuwamoto et al.

Enokida et al. (2001) have reported that thedecreased proximal tibial cortical BMD in adult
CIA rats might be related to changes of the periosteal bone surface and the intracortical bone.
Hayashida et al. (1993) have histologically examined the cortical bone adjacent to the affectedjoint in adjuvant arthritis rats, and reported thatboth the bone resorption and inflammatory cellinﬁltration were increased around the intracortical
blood vessels, which was similar to histologicalﬁndings of juxtaarticular osteoporosis in patientswith RA. The immobilization-related decrease in
the cortical BMD is considered to be associatedwith a disorder of periosteal modeling-dependentbone gain and an enhancement of endocorticaland intracortical bone remodeling-dependent boneloss (Li et al., 1991; Jee et al., 1992; Maeda et al.,1993). Yonezu et al. (2004) have reported that
sciatic neurectomy decreased mechanical stresson the bone around paralyzed muscles and reduced periosteal bone formation, thus causing thedecrease in the cortical BMD. Since the corticalbone loss mechanism in CIA rats may be different
from that linked to immobilization, it is speculated that the cortical bone loss in the CIA+NTx
group was greater than in the CIA group.
In summary, the present study revealed thatsciatic neurectomy reduced the severity of arthritis, but did not affect the cancellous bone loss inadult CIA rats. It is speculated that limitations ofmovement due to paralysis reduces exercise stress,
which thus ultimately suppresses arthritis.

2003). Okumura et al. (1987) have reported a reduction in the BMD of ovariectomized rats, which
deteriorated after sciatic neurectomy. We assumedin the present study that periarticular bone loss
deteriorated in CIA + NTx rats as well. To evaluate this hypothesis, we examined the effects ofsciatic neurectomy on arthritis and the BMD in
CIA and CIA+NTx rats.
Kozina et al. (1977) have reported the effectsof peripheral nerve and spinal lesions on arthritis
in adjuvant arthritis rats. They found that peripheral nerve and spinal lesions suppressed hindpaw swelling and suggested that the effect wasdue to hind paw paralysis. In our study, sciatic
neurectomy reduced hind paw swelling and ankle
and subtalar joint destruction in CIA rats. Many
reports have described that paralysis suppressed
RA, osteoarthritis and arthritis and radiological joint destruction caused by gout in humans(Coste et al., 1935; Bland et al., 1968; Pattrick etal., 1984). Bland et al. (1968) and Pattrick et al.
(1984) stated that the restriction of movement due
to paralysis may reduce mechanical stress, resulting in the suppression of arthritis. In many casesof osteoarthritis and RA, arthritis is severer in thedominant hands than in the non-dominant hands,suggesting that exercise stress has a signiﬁcant effect on the severity of arthritis.
The occurrence of periarticular bone loss
in arthritis is suggested to be related to synovitis associated with arthritis (Suzuki et al., 1995)
and bone marrow lesions in the peripheral bones(Fujimoto et al., 1992; Enokida et al., 2001). In
immobilized tibia after sciatic neurectomy inmice, a temporary increase in bone resorption
and a continuing decrease in bone formation
caused rapid cancellous bone loss (Sakai A etal., 1996). We assumed that immobilization due
to sciatic neurectomy might deteriorate cancellous bone loss in the CIA+NTx group; however,there was no signiﬁcant difference in the degreeof cancellous bone loss between the CIA and theCIA+NTx groups. The reason for this may be that
arthritis was suppressed by sciatic neurectomy in
the CIA+NTx group, which reduced the degree ofsynovitis due to arthritis.

Acknowledgments: We are grateful to Professor Tatsuo
Watanabe, Division of of Integrative Physiology, Department of Functional, Morphological and Regulatory
Science, and Professor Chiaki Shigemasa, Division ofMolecular Medicine and Therapeutics, Department ofMultidisciplinary Internal Medicine, School of Medicine,
Tottori University Faculty of Medicine, for their criticalreadings of the present manuscript. We deeply thankProfessor Ryota Teshima, Division of Orthopaedic Surgery, Department of Medicine of Sensory and MotorOrgans, School of Medicine, Tottori University Facultyof Medicine, for encouraging us in achieving this study
and for giving us invaluable advice.

62

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Received June 4, 2007; accepted August 20, 2007
Corresponding author: Toru Okano, MD63