Microinjection of codeine into the region of the caudal ventral respiratory column suppresses cough in anesthetized cats

Abstract

We investigated the influence of microinjection of codeine into the caudal ventral respiratory column (cVRC) on the cough reflex. Experiments were performed on 36 anesthetized spontaneously breathing cats. Electromyograms (EMGs) were recorded bilaterally from inspiratory parasternal and expiratory transversus abdominis (ABD) muscles and unilaterally from laryngeal posterior cricoarytenoid and thyroarytenoid muscles. Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airways. The unilateral microinjection of codeine (3.3 mM, 20–32 nl) in the cVRC reduced cough number by 29% ( P < 0.01) and expiratory cough amplitudes of esophageal pressure by 33% ( P < 0.05) as well as both ipsilateral and contralateral ABD EMGs by 35% and 48% ( P < 0.01 and P < 0.01, respectively). No cough depression was observed after microinjections of vehicle. There was no significant effect of microinjection of codeine in the cVRC (3.3 mM, 30–40 nl) on ABD activity induced by a microinjection of d,l-homocysteic acid (30 mM, 27–40 nl) in the same location. However, a cumulative dose of codeine (0.1 mg/kg, 330 nmol/kg) applied into the brain stem circulation through the vertebral artery reduced the ABD motor response to cVRC d,l-homocysteic acid microinjection (30 mM, 28–32 nl) by 47% ( P < 0.01). These results suggest that 1) codeine can act within the cVRC to suppress cough and 2) expiratory premotoneurons within the cVRC are relatively insensitive to this opioid.