Abstract
Bradykinin (Bk) is a potent inflammatory mediator that causes hyperalgesia. The action of Bk on the sensory system is well documented but its effects on motoneurons, the final pathway of the motor system, are unknown. By a combination of patch-clamp recordings and two-photon calcium imaging, we found that Bk strongly sensitizes spinal motoneurons. Sensitization was characterized by an increased ability to generate self-sustained spiking in response to excitatory inputs. Our pharmacological study described a dual ionic mechanism to sensitize motoneurons, including inhibition of a barium-sensitive resting K(+) conductance and activation of a nonselective cationic conductance primarily mediated by Na(+). Examination of the upstream signaling pathways provided evidence for postsynaptic activation of B2 receptors, G protein activation of phospholipase C, InsP3 synthesis, and calmodulin activation. This study questions the influence of motoneurons in the assessment of hyperalgesia since the withdrawal motor reflex is commonly used as a surrogate pain model.
Keywords:
hyperalgesia; motoneuron; neuroscience; pain; rat; spinal cord.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Action Potentials / drug effects
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Animals
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Animals, Newborn
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Bradykinin / pharmacology*
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Calcium / metabolism
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Calmodulin / genetics
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Calmodulin / metabolism
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Female
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Ganglia, Spinal / cytology
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Ganglia, Spinal / drug effects*
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Ganglia, Spinal / metabolism
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Gene Expression
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Hyperalgesia / chemically induced
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Hyperalgesia / genetics
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Hyperalgesia / metabolism*
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Hyperalgesia / pathology
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Inflammation / chemically induced
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Inflammation / genetics
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Inflammation / metabolism
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Inflammation / pathology
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Inositol 1,4,5-Trisphosphate / biosynthesis
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Male
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Molecular Imaging
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Motor Neurons / cytology
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Motor Neurons / drug effects*
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Motor Neurons / metabolism
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Pain / chemically induced
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Pain / genetics
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Pain / metabolism*
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Pain / pathology
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Patch-Clamp Techniques
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Potassium Channels / genetics
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Potassium Channels / metabolism
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Rats
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Rats, Wistar
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Receptor, Bradykinin B2 / genetics
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Receptor, Bradykinin B2 / metabolism
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Signal Transduction
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Sodium Channels / genetics
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Sodium Channels / metabolism
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Spinal Cord / cytology
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Spinal Cord / drug effects
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Spinal Cord / metabolism
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Type C Phospholipases / genetics
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Type C Phospholipases / metabolism
Substances
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Calmodulin
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Potassium Channels
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Receptor, Bradykinin B2
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Sodium Channels
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Inositol 1,4,5-Trisphosphate
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Type C Phospholipases
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Bradykinin
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Calcium
Grants and funding
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.