Proceedings of The Physiological Society
Durham University (2010) Proc Physiol Soc 21, C09 and PC09
Mechanically evoked spinal reflexes are augmented in a rat model of osteoarthritic pain
S. Kelly1, G. Allen2, J. Harris2
1. Arthritis Research UK Pain Centre, School of BIosciences, University of Nottingham, Nr Loughborough, United Kingdom. 2. School of Biosciences, University of Nottingham, Nr Loughborough, United Kingdom.
Osteoarthritis (OA) is a degenerative joint disease that leads to chronic pain; the mechanisms of which are unclear. OA patients show an expanded original pain area and hyperalgesia at distant sites (Arendt-Nielsen et al., 2010). The monoiodoacetate (MIA) rat model of OA (Bove et al., 2003) is associated with both joint pain and hypersensitivity of distal sites (hind-paw). It is possible that central sensitization underlies the behavioural hypersensitivity in this model, and human OA pain. Indeed, lower limb spinal reflex responses are augmented in human OA knee pain (Courtney et al., 2009, 2010). We have investigated whether spinal reflexes are sensitized in the MIA model. MIA (1mg/50microl; n=7) or saline (50microl; n=7) was injected intra-articularly (left knee) of male wistar rats under isoflurane anaesthesia (3% in O2). 28 days post-MIA/saline, rats were re-anesthetised (induction - 3% isoflurane in N2O/O2; maintenance - alfaxan 1.3ml/hr, iv) for recording of ipsilateral hindlimb reflexes (Clarke and Harris 2004). Reflexes were evoked by hindpaw mechanical stimulation with von Frey monofilaments (3s each) or by electrical stimulation at the heel or toes. Hindpaw receptive fields of tibialis anterior (TA, ankle flexor) and biceps femoris (BF, knee flexor) reflexes were mapped (60g von Frey). Then the mechanical threshold and stimulus response function (4-60g von Frey) of TA and BF reflexes were ascertained. The electrical threshold to evoke reflexes in TA, BF and medial gastrocnemius (MG, ankle extensor) as well as the reflex latency were measured. Finally, ‘wind-up’ of reflexes was studied (8 stimuli, 1 Hz, 1 ms, 10 mA). MIA resulted in reduced ipsilateral weight bearing (day 3-28; p<0.001; two-way ANOVA). The hindpaw receptive field size for TA and BF reflexes showed a tendency to decrease and increase respectively in MIA rats compared to saline rats. BF hind-paw mechanically evoked reflexes were facilitated in MIA rats compared to saline rats. The threshold was significantly reduced (median= 15 vs 60g, MIA vs saline, p<0.05, Mann Whitney) and the stimulus response curve was significantly augmented (p<0.05, two-way ANOVA, MIA vs saline). No significant differences were observed in electrical thresholds and latencies of spinal reflexes in MIA compared to saline rats. However, the wind-up of the C-fibre component of reflexes to repetitive electrical stimulation appeared to be increased in MIA rats. We report that the excitability of spinal nociceptive reflexes is increased in a model of OA pain. The facilitation of reflex responses is thought to represent the physiological basis in the motor system for allodynia and hyperalgesia indicating that central sensitization is likely to be responsible at least in part for the pain behaviour exhibited.
Where applicable, experiments conform with Society ethical requirements