Intrathecal pertussis toxin produces hyperalgesia and allodynia in mice

Abstract

Pertussis toxin (PTX), which causes the ADP-ribosylation and thereby inactivation of G i-proteins, has been employed in analgesia testing to elucidate receptors that are coupled to inhibitory G-proteins, such as the mu-opioid receptor. Consistent with previous findings, the antinociceptive effects of morphine (1–10 μg) as measured by tail-flick latency using a 55°C water bath, were blocked by a single intrathecal injection of 0.5 μg PTX 6 days prior to intrathecal morphine administration. In addition, mice treated intrathecally with 0.5 μg of PTX had significantly shorter baseline tail-flick latencies compared with vehicle treated mice using a 55°C water bath when tested 6 days after PTX or vehicle administration. Morphine-induced antinociception was blocked in a dose-dependent manner by PTX with complete blockade of morphine following a 0.3- μg dose of PTX. Further, mice administered 0.1 μg or 0.3 μg PTX intrathecally had significantly shorter tail-flick latencies compared with vehicle injected mice using a 40, 45 or 50°C water bath when tested 7 days after intrathecal injection. Shorter tail-flick latencies were observed at 45°C as early as 48 h after intrathecal administration of 0.03, 0.1 or 0.3 μg PTX and these shorter tail-flick latencies were observed up to 90 days after intrathecal PTX administration. The intrathecal administration of PTX caused hyperalgesia and allodynia that appears similar to the symptoms reported by patients suffering from neuropathic pain, and suggests that deficiencies in inhibitory systems, as compared with increases in excitatory systems, may play a role in the pathophysiology of at least some central or neuropathic pain states.