Background and Purpose: Brain neurovascular coupling (NVC) involves voltage-gated Ca++ channels (VGCC) and prostaglandins. However, their differential contribution in the spinal cord neurovascular coupling (NVC) is unknown. This study used non-invasive functional near infrared spectroscopy (fNIRS) to assess how ibuprofen (COX inhibitor) and pregabalin (VGCC α2δ subunit binder) affect human perispinal neurovascular responses (NVR). Experimental Aproach: Perispinal cervical and lumbar NVRs elicited by painless electrical stimulation of the posterior tibial nerve were recorded using a non-invasive fNIRS technique before and 60 minutes after oral administration of a single clinical dose of 10mg∙kg-1 IBU (n=38) or 75 mg PGL (n=32) in healthy volunteers. Key Results: IBU reduced the NVR amplitude by 17% (Lumbar) and 34% (Cervical), rise time by 20% (Lumbar) and 25% (Cervical), and duration by 12% (Lumbar) and 20% (Cervical). PGL reduces the amplitude of perispinal NVR by 35% (Lumbar) and 70% (Cervical) and its duration by 20% (Lumbar) and 30% (Cervical). Conclusion and Implications: These results demonstrate the differential pharmacological intensity effect of clinical dose of IBU or PGL across cervical and lumbar spinal cord levels, but also contribution of the neuronal excitability, mediated by Ca++ channels, and prostaglandins in the perispinal NVR. Furthermore, they underscore the potential of the fNIRS for monitoring the pharmacological effects of IBU and PGL on the human spinal cord.