Background: A wide range of stimuli can activate sensory neurons and neurons innervating specific tissues often have distinct properties. Here we used retrograde tracing to identify sensory neurons innervating the hind paw skin (cutaneous) and ankle/knee joints (articular), and combined immunohistochemistry and electrophysiology analysis to determine the neurochemical phenotype of cutaneous and articular neurons, as well as their electrical and chemical excitability.

Results: Immunohistochemistry analysis using RetroBeads as a retrograde tracer confirmed previous data that cutaneous and articular neurons are a mixture of myelinated and unmyelinated neurons, and the majority of both populations are peptidergic. In whole-cell patch-clamp recordings from cultured dorsal root ganglion neurons, voltage-gated inward currents and action potential parameters were largely similar between articular and cutaneous neurons, although cutaneous neuron action potentials had a longer half-peak duration. An assessment of chemical sensitivity showed that all neurons responded to a pH 5.0 solution, but that acid-sensing ion channel (ASIC) currents, determined by inhibition with the non-selective ASIC antagonist benzamil, were of a greater magnitude in cutaneous compared to articular neurons. 40 – 50% of cutaneous and articular neurons responded to capsaicin, cinnamaldehyde and menthol, indicating similar expression levels of TRPV1, TRPA1 and TRPM8 respectively. By contrast, significantly more articular neurons responded to ATP than cutaneous neurons.

Conclusion: This work makes a detailed characterization of cutaneous and articular sensory neurons, and highlights the importance of making recordings from identified neuronal populations: sensory neurons innervating different tissues have subtly different properties, possibly reflecting different functions.