Biomarkers of Neuropathic Pain

They can be used to access neuropathic pain, diagnostics, clinical trials and in assessing therapeutic intervention for treating pain

Background

Pain is a sensory disturbance that is very difficult to measure accurately based on patients' subjective reports. There is an enormous need for objective and sensitive biomarkers of pain–especially by industry for clinical trials for the development of novel analgesics, but also clinically to assess the presence and extent of pain in individual patients. There are no such biomarkers at present.

Technology Overview

The researchers found that nerve injury causes a significant 50% increase in brief awakenings (2-30 s) that disrupt sleep continuity and cause sleep fragmentation, which resolves when the evoked pain sensitivity returns to pre-injury values. The increase in sleep fragmentation enables objective detection and quantification of the presence and degree of spontaneous neuropathic pain and can be utilized as a biomarker for unbiased determination of the relevance of biological targets or the efficacy of pharmacological drugs for the spontaneous pain caused by nerve injury.

Stage of Development

• Proof of Concept.
• Transgenic mice where peripheral nociceptors (peripheral pain causing fibers) are genetically silenced do not develop the sleep fragmentation after nerve injury, indicating that these neurons are the source of the input that causes the abnormal degree of sleep fragmentation.
• Administration of analgesics drugs (gabapentin, carbamazepine) dose-dependently normalize sleep fragmentation in mice with efficacy at doses active in patients with neuropathic pain.
• Figure 1.

Further Details

Alexandre, C., Latremoliere, A., Ferreira, A. et al. Decreased alertness due to sleep loss increases pain sensitivity in mice. Nat Med 23, 768–774 (2017). https://doi.org/10.1038/nm.4329

Benefits

Provides methods of objectively detecting and measuring neuropathic pain in a subject.

Applications

• Neuropathic pain measurement
• Assessment of therapeutic intervention for treating pain
• Diagnostics
• Clinical trials

IP Status

• Patent application submitted