EFFECTS OF GABA-B AGONIST BACLOFEN ON BRONCHIAL HYPERREACTIVITY TO INHALED HISTAMINE IN SUBJECTS WITH CERVICAL SPINAL-CORD INJURY

Bronchial provocation studies performed in our research center have co nsistently demonstrated airway hyperresponsiveness to both inhaled met hacholine and histamine in subjects with chronic cervical spinal cord injury (SCI). More recently, we reported that the airways of such subj ects maintained on chronic baclofen (gamma-aminobutyric acid) therapy were not hyperreactive to inhaled methacholine. In this study we deter mined whether baclofen also blocks the effects of the bronchoprovocati ve agent histamine in subjects with cervical SCI, Twenty-four male sub jects with cervical SCI participated in this study; 14 were maintained on oral baclofen, and 10 served as age-matched controls. The subjects were challenged with increasing concentrations of aerosolized histami ne until either a 20% fall in forced expiratory volume in 1 s (FEV1) f rom baseline (defined as PC20) was observed, or a maximum of 25 mg/ml histamine was administered. We found that 11 of the 14 baclofen subjec ts (78.5%) and 8 of the 10 control subjects (80%) responded (PC20 < 8 mg/ml) to the histamine challenge. Mean PC20 values among responders i n the baclofen (PC20 = 2.91 +/- 2.3) and control (PC20 = 2.18 +/- 1.9) groups did not differ significantly. Because histamine acts directly on histamine receptors and indirectly on cholinergic pathways, our fin dings that baclofen blocks bronchoconstriction due to inhaled methacho line, but not that due to histamine, suggests that hyperresponsiveness in subjects with cervical SCI may be secondary to nonspecific airway hyperreactivity.