Intrathecal pertussis toxin induces thermal hyperalgesia: Involvement of excitatory and inhibitory amino acids

Intrathecal pertussis toxin injection has been used as a neuropathic pain model. In the present study, its effects on cerebrospinal fluid biochemistry and nociceptive behavioral expression were examined in rats. Cerebrospinal fluid dialysate samples were collected and pertussis toxin was injected using an intrathecally implanted dialysis loop catheter; samples were collected and hyperalgesia behavior was noted every 2 days for 8 days after pertussis toxin injection. Pertussis toxin injection induced thermal hyperalgesia which peaked between day 2 and 4; no cold allodynia was observed. Pertussis toxin at all doses tested (0.5, 1, or 2 μg) also induced a significant increase in cerebrospinal fluid concentrations of aspartate and glutamate between days 2 and 8, while level of the inhibitory amino acid glycine were significantly decreased by the two higher doses of pertussis toxin. Intrathecal administration of the N-methyl-D-aspartate receptor antagonist D-2-amino-5-phosponovaleric acid (10 μg) or glycine (200 μg), inhibited pertussis toxin-induced thermal hyperalgesia. Pertussis toxin injection had no effect on serine, glutamine, and taurine concentrations. These results show that intrathecal pertussis toxin injection induces thermal hyperalgesia and it is associated with an increasing of excitatory and a decreasing of inhibitory amino acids release in the spinal cord.