1. Although
sodium channel blockers are effective
analgesics in
neuropathic pain, their effectiveness in inflammatory
pain has been little studied.
Sodium channels are substantially up-regulated in inflamed tissue, which suggests they play a role in maintenance of chronic inflammatory
pain. We have examined the effects of
sodium channel blockers on mobility, joint
hyperalgesia and
inflammation induced by complete
Freund's adjuvant injected in one ankle joint of adult rats. The clinically effective
sodium channel blocker,
mexiletine, was compared with
crobenetine (
BIII 890 CL), a new, highly use-dependent
sodium channel blocker. 2. Rats were treated for 5 days, starting on the day of induction of
arthritis and were tested daily for joint
hyperalgesia, hind limb posture and mobility. At post-mortem, joint stiffness and oedema were assessed. Dose response curves were constructed for each test compound (3 - 30 mg kg day(-1)). Control groups were treated with vehicle or with the non-steroidal anti-inflammatory
drug,
meloxicam (4 mg kg day(-1) i.p.). 3. Both
sodium channel blockers produced dose dependent and significant reversal of mechanical joint
hyperalgesia and impaired mobility with an ID50 of 15.5+/-1.1 mg kg day(-1) for
crobenetine and 18.1+/-1.2 mg kg day(-1) for
mexiletine. Neither compound affected the responses of the contralateral non-inflamed joint, nor had any effect on swelling and stiffness of the inflamed joint. 4. We conclude that
sodium channel blockers are
analgesic and anti-hyperalgesic in this model of
arthritis. These data suggest that up regulation of
sodium channel expression in primary afferent neurones may play an important role in the
pain and
hyperalgesia induced by joint
inflammation.