Most preclinical neuroscience programs are still built around two categories of evidence. Behavior tells you what the animal does, and histology tells you what the tissue looks like at the end. Both are necessary, and neither is sufficient on its own. Behavior is sensitive but noisy, shaped by handling, environment, and the inherent variability of how an animal expresses discomfort or impairment. Histology is precise but terminal, a snapshot taken after the biology of interest has already played out. Between these two sits a third category that programs underuse, and that category is functional electrophysiology. Nerve conduction studies, evoked potentials, and electroretinography measure the nervous system while it is working, and they do so on scales that map directly onto the instruments a neurologist or ophthalmologist uses in the clinic.
That last point is what makes electrophysiology valuable as a translational tool rather than a laboratory curiosity. When a clinician evaluates a patient with peripheral neuropathy, the objective measurement is a nerve conduction study. When a clinician assesses optic pathway integrity in multiple sclerosis, the measurement is a visual evoked potential. A preclinical endpoint that uses the same physical readout in an animal model, rather than a species specific behavioral proxy, removes one of the translation steps where preclinical to clinical concordance tends to break down.
The electrophysiology suite spans the sensory and motor systems and the special senses. Sensory nerve conduction velocity and the sensory nerve action potential characterize peripheral sensory function and are the natural readouts for neuropathy severity. The compound muscle action potential reads motor nerve function and neuromuscular junction integrity. Motor and sensory evoked potentials, recorded transcranially as tcMEP and tcSEP, interrogate corticospinal and somatosensory pathway integrity, which is why they are central to spinal cord injury and multiple sclerosis work. Electroretinography and visual evoked potentials extend the same logic to the retina and the optic pathway, capturing deficits in models where the visual system is affected either as a primary target or as an accessible window onto central function.
The value of running several of these in parallel is that they triangulate. A behavioral change with a concordant shift in nerve conduction is a more defensible finding than either alone, and a divergence between the two is itself informative about mechanism. In a streptozotocin rat model of diabetic neuropathy, for instance, sensory nerve conduction velocity is significantly reduced relative to naive animals, and electroretinography and visual evoked potential amplitudes are significantly diminished by four months after induction. Those functional deficits anchor the behavioral and histological findings in measurements that a clinical team recognizes immediately.
Several of these modalities are routine in rodents and have been for decades. Establishing them in pigs was not a matter of scaling up the same recording. MD Biosciences developed the first compound muscle action potential and sensory nerve action potential recordings in swine, which sounds incremental until you consider what the pig brings to a pain or neuropathy program. Porcine peripheral neurophysiology overlaps almost completely with human peripheral neurophysiology, a point established in the Meijs systematic review of porcine pain models, and the pig expresses spontaneous, observable pain behaviors that rodents do not. Bringing electrophysiology into that animal means a single study can yield behavior, nerve conduction, and histology from the same subject, in a species whose nervous system is built much more like a human's than a rat's is.
That combination matters most when the question is functional. A program developing a peripheral nerve therapeutic, an analgesic with a suspected conduction effect, or a candidate where neurotoxicity is a liability gains more from a conduction measurement in a large animal than from a behavioral score alone, because the conduction measurement is the same quantity the eventual clinical program will track.
Functional recording is also a route to new biomarkers, not only a way to reproduce established ones. Work in the MOG-EAE model, in which experimental autoimmune encephalomyelitis is induced by immunization against myelin oligodendrocyte glycoprotein, identified a novel sensory evoked potential component occurring roughly 25 milliseconds after stimulation, designated the P25 wave. In animals with mild disease the P25 amplitude increases, tracking a hypersensitivity state and correlating with vocalization, and morphine reduces it. As disease becomes severe, the wave is lost entirely as motor and sensory function collapse. Described by Shulman and colleagues in the Journal of Pain, the P25 wave is the first quantitative in vivo electrophysiological biomarker of pain related hypersensitivity in a multiple sclerosis model, and it exists because the recording platform was sensitive enough to resolve it. Endpoints like this do not emerge from behavior or histology; they emerge when you are measuring the live nervous system with enough resolution to notice something new.
Electrophysiology earns its place when a program needs an objective, translatable readout of nervous system function, and it earns it across more disease areas than teams often assume. Peripheral neuropathy, chemotherapy induced neuropathy, diabetic neuropathy, spinal cord injury, multiple sclerosis, and models with a retinal or optic component all have a natural functional endpoint waiting to be measured. The practical advantage is integration. These recordings are non terminal, so they can be collected longitudinally across a study and then anchored to terminal histology and biomarker readouts from the same animals, which tightens the internal consistency of the dataset and reduces the number of animals a program needs to answer its question.
For sponsors weighing whether a functional endpoint would strengthen a neuroscience or pain package, MD Biosciences runs the full electrophysiology suite, from rodent to pig, in the same facility that handles the behavioral and histological work. Questions about study design are welcome at neuro@mdbiosciences.com.
References:
Meijs S et al. 2021. A systematic review of porcine models in translational pain research. Lab Animal. (Meilin co-author.)
Shulman Y et al. A Novel Sensory Wave (P25) in Myelin Oligodendrocyte Glycoprotein-induced Experimental Autoimmune Encephalomyelitis Murine Model. Journal of Pain. (Castel and Meilin co-authors.)