How does pain disrupt sleep?
One major goal of our research is to understand the neural plasticity caused by peripheral nerve injury and how this leads to an abnormal, chronic pain state known as neuropathic pain. Neuropathic pain occurs in up to 50% of patients after nerve trauma, and it is characterized by abnormal pain symptoms, such as hyperalgesia (more pain to noxious stimuli), allodynia (pain in response to innocuous stimuli), and spontaneous pain (pain in absence of external stimuli). To deconstruct the neural circuits responsible for each of these symptoms, we employ cre-recombinase-mediated cell-specific expression of toxins and inducible chemogenetic methods for silencing and channelrhodopsin expression for activating neurons, and determine the consequences on behavioral (pain reflexive and operant tests) and physiological (sleep) readouts.
Discovering new analgesic treatments
Current treatments for neuropathic pain are poorly effective with numerous adverse side effects and most attempts to develop new analgesics have failed. Therefore, there is a critical need to identify novel pharmacological targets. Both human and mouse genetic studies have demonstrated a critical role of the tetrahydrobiopterin (BH4) production pathway in neuropathic pain. We are testing if systematically modulating BH4 production by targeting the enzyme sepiapterin reductase (SPR) represents a viable therapeutic strategy to reduce pain hypersensitivity and other nerve injured-induced changes without causing major side effects.
How does sleep loss increase pain sensitivity?
Chronic sleep loss is common in modern societies despite increasing evidence that even mild chronic sleep deprivation disrupts a wide range of neurobehavioral and physiological functions, including pain. While the existence of a “vicious” cycle between lack of the sleep and increased pain has reliably been shown, very little is known about the underlying mechanisms. Together with Dr. Chloe Alexandre we are using behavioral, anatomical and genetic techniques to identify the precise neural links between sleep and pain in mice. By analyzing sleep-wake behaviors using EEG/EMG signals in mouse models of chronic pain, we aim to understand how chronic pain affects sleep.