Effects of Spinal Cord Superfusion with Substance P on the Excitability of Rat Dorsal Horn Neurons Processing Input from Deep Tissues

Abstract

Objectives: Starting from the clinical finding that in fibromyalgia patients the concentration of substance P [SP] in the cerebrospinal fluid is increased, the study aimed at determining the influence of intrathecally administered SP on the excitability of dorsal horn neurons. Methods: In anesthetized rats, the discharges of single dorsal horn neurons in response to electrical stimulation of peripheral nerves and mechanical stimulation of receptive fields [RFs] were recorded. Only those neurons were studied that had excitatory input from non-proprioceptive receptors in deep tissues. The influence of SP on the excitability of the cells was determined by superfusing the spinal cord with SP at defined concentrations. Results: The main effects of SP were: 1. Increase in the number of peripheral nerves and/or afferent fiber types that were effective in driving the dorsal horn neurons. 2. Increase in the size or number of mechanosensitive RFs in nociceptive neurons. 3. Loss of an existing response to peripheral input. The SP-induced effects were dose-dependent, the threshold concentration in the superfusate being 1-10 µM. Intracellular recordings showed that in the presence of SP subthreshold excitatory postsynaptic potentials became suprathreshold. Conclusions: The results demonstrate that inrathecal SP affects dorsal horn neurons in different ways. One important action of the neuropeptide is to unmask synaptic connections in the dorsal horn. The data are compatible with the assumption that SP is involved in neuroplastic changes in the dorsal horn. The increase in RF size in nociceptive cells may be a possible mechanism for hyperalgesia in patients with deep pain.

KEYWORDS:

• Substance P
• neuronal excitability
• dorsal horn neurons
• neuroplasticity
• deep pain