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Stellate ganglion block has been extensively used in clinical practice for the management of painful conditions such as cephalic, facial and upper limb pains yet its mechanism of action and its analgesic efficacy are poorly understood.Formalin (3% 0.2 mL) was injected into the plantar region of the right upper limb paw in rabbits and 50 min after this injection, saline or bupivacaine 2.5% 0.5 mL was administered via a chronic implantation catheter near the right stellate ganglion. Behavioural modification, changes in heart rate and plasma norepinephrine release at different time points after formalin and bupivacaine or saline injection were observed. Finally, the cervical spinal cord was harvested and immunostaining for substance P and c-Fos was performed.Formalin caused stress noxious behavioural changes and a significant increase in heart rate and norepinephrine release. These changes were inhibited by bupivacaine stellate ganglion block but not by saline injection. Immunoreactants of substance P were significantly decreased by formalin injection compared with that in controls. However, with bupivacaine injection, substance P levels were restored though not reaching the levels seen in the controls. Formalin injection also caused a significant increase of c-Fos expression in cervical spinal cord. This increase was not affected by stellate ganglion block.Stellate ganglion block can effectively alleviate nociceptive responses induced by formalin injection. The mechanism of its action may involve reduction of substance P in the spinal cord and plasma catecholamine release caused by noxious stimuli.