Intrathecal Bradykinin Administration: Opposite Effects on Nociceptive Transmission

Abstract

Injected intrathecally, bradykinin (BK) produced either hyperalgesia (0.15 µg) or antinociception (6.0 µg) in rats when thermal noxious stimuli were used. Similarly, des-Arg⁹-BK at the lower dose (0.15 µg) decreased, whereas at the higher dose (6.0 µg) it increased the threshold to thermal noxious stimuli; however, these effects were less pronounced than those of BK. The antinociception induced by BK was abolished by HOE 140, a B₂ receptor antagonist, injected intrathecally at a dose of 1.3 ng and was markedly attenuated by des-Arg¹⁰-HOE 140, a B₁ receptor antagonist (1.15 ng i.t.). The results obtained in this study showed that – depending on the dose used – BK and des-Arg⁹-BK could produce pro- as well as antinociceptive actions. Both B₂ and B₁ receptors are involved in the action of intrathecally applied BK.

Spinal Dynorphin and Bradykinin Receptors Maintain Inflammatory Hyperalgesia

“…administration of bradykinin. The reported outcome of this approach varies widely, ranging from transient antinociceptive effect in animals within one minute and the effect lasted less than 15 minutes 25,34, to long lasting hyperalgesia (up to 4 hr) that peaked at 90 min23,46. We could not detect any hyperalgesic effect induced by intrathecal bradykinin at the dose range as previously reported46 and measured with three behavioral tests (Fig.…”

Pronociceptive actions of dynorphin via bradykinin receptors

“…Prior reports on intrathecal injection of bradykinin have yielded conflicting nociceptive behavior, ranging from transient hyperalgesia followed by increased thermal latency in the tail flick test attributed to the release of norepinephrine [21], to long lasting hyperalgesia that peaks at 75 min and slowly recovers over 4 hr [51]. The effect of bradykinin also appears to vary with dose, which was found to be hyperalgesic at low dose, but antinociceptive at high dose [35].…”

Kinin B1 receptors: key G‐protein‐coupled receptors and their role in inflammatory and painful processes

“…In fact, intrathecal administration of B 1 receptor agonists induces hyperalgesia after peripheral thermal or mechanical stimulation in mice and rats ( Ferreira et al ., 2002 ; Fox et al ., 2003 ). In addition, the B 1 receptor seems to be involved in the late component of the hyperalgesia induced by bradykinin, a potent activator of C fibres ( Ferreira et al ., 2002 ; Sot et al ., 2002 ). Moreover, repetitive electrical stimulation of the dorsal root produces an increase in the VRP, a use‐dependent facilitation plasticity of the spinal cord neurones named wind‐up.…”