High voltage
calcium channels are implicated in nociceptive transmission after nerve injury,
capsaicin or
formalin injection. The purpose of this study was to investigate the role of
calcium channels in secondary heat
hyperalgesia associated with acute joint
inflammation. After induction of acute
inflammation (knee joint injection of
kaolin and
carrageenan), decreased paw withdrawal latency (PWL) to radiant heat (i.e., secondary heat
hyperalgesia), increased guarding of the limb and increased joint circumference occurs. Spinal administration (through a microdialysis fiber placed in dorsal horn) of an
N-type calcium channel blocker (MVIIA,
SNX 111,
ziconotide, 0.001-0.1 mM), before induction of
inflammation, prevents the decrease in PWL. Treatment with
SNX 111 4 hr after
inflammation reverses heat
hyperalgesia. A small reduction in spontaneous
pain-related behaviors (guarding of the limb) occurs after pre- or post-treatment with
SNX 111. Spinal blockade of P/
Q-type calcium channels (with
omega-agatoxin IVA) had no effect on the decrease in PWL to radiant heat when administered after induction of
inflammation. However, pre-treatment with
omega-agatoxin IVA prevents secondary heat
hyperalgesia.
omega-Agatoxin IVA has no effect on spontaneous
pain-related behaviors whether administered before or after induction of
inflammation. In contrast, pre or post-treatment with
nifedipine (
L-type calcium channel blocker, 0.01-1.0 mM), had no effect on heat
hyperalgesia or spontaneous
pain-related behaviors induced by acute
inflammation. There were no differences in joint circumference between groups with any treatment. Thus,
N-type calcium channels contribute to both the development and maintenance of secondary heat
hyperalgesia while
P-type calcium channels are only involved during development of
hyperalgesia.