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The cerebellum plays a major role in not only modulating motor activity, but also contributing to other functions, including nociception. The intermediate hemisphere of the cerebellum receives sensory input from the limbs. With the extensive connection between the cerebellum to brain-stem structures and cerebral cortex, it is possible that the cerebellum may facilitate the descending system to modulate spinal dorsal horn activity. This study provided the first evidence to support this hypothesis. Thirty-one wide-dynamic-range neurons from the left lumbar and 27 from the right lumbar spinal dorsal horn were recorded in response to graded mechanical stimulation (brush, pressure, and pinch) at the hind paws. Electrical stimulation of the cerebellar cortex of the left intermediate hemisphere significantly reduced spinal cord dorsal horn neuron-evoked responses bilaterally in response to peripheral high-intensity mechanical stimuli. It is concluded that the cerebellum may play a potential antinociceptive role, probably through activating descending inhibitory pathways indirectly.

Neurostimulation of the spinal cord or brain has been used to inhibit nociceptive signals in pain management applications. Nevertheless, most of the current neurostimulation models are based on open-loop system designs. There is a lack of closed-loop systems for neurostimulation in research with small freely-moving animals and in future clinical applications. Based on our previously developed analog wireless system for closed-loop neurostimulation, a digital wireless system with real-time feedback between recorder and stimulator modules has been developed to achieve multi-channel communication. The wireless system includes a wearable recording module, a wearable stimulation module and a transceiver connected to a computer for real-time and off-line data processing, display and storage. To validate our system, wide dynamic range neurons in the spinal cord dorsal horn have been recorded from anesthetized rats in response to graded mechanical stimuli (brush, pressure and pinch) applied in the hind paw. The identified nociceptive signals were used to automatically trigger electrical stimulation at the periaqueductal gray in real time to inhibit their own activities by the closed-loop design. Our digital wireless closed-loop system has provided a simplified and efficient method for further study of pain processing in freely-moving animals and potential clinical application in patients.

We implemented an integrated system that can acquire neuronal signals from spinal cord dorsal horn neurons, wirelessly transmit the signals to a computer, and recognize the nociceptive signals from three different mechanical stimuli (brush, pressure and pinch). Positive peak detection method was chosen to distinguish between signal spikes. The inter spike intervals (ISIs) were calculated from the identified action potentials (APs) and fed into a numerical array called cluster. When the sum of the ISIs in the cluster reached a critical level, the program recognized the recorded signals as nociceptive inputs. The user has the flexibility to tune both the cluster size and critical threshold for individual's need to reach optimization in pain signal recognition. The program was integrated with a wireless neurostimulator to form a feedback loop to recognize and inhibit nociceptive signals.

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