How ion channels speak the language of pain
With one in three adults experiencing chronic pain in their lives and treatments of limited efficacy, all fueling the growing opioid crisis, our understanding of the balance between pain and chronic pain, and how we treat pain becomes increasingly important.
Nociception - the body's way of sensing pain
Ion channels are central to both the physiological pain response and the pathophysiological changes that underlie chronic pain. These specialized protein structures, embedded in cellular membranes, regulate the flow of ions such as sodium (Na⁺), potassium (K⁺), and calcium (Ca²⁺) across the cell membrane. This ionic movement generates electrical signals that propagate along neurons, ultimately reaching the brain where they are perceived as pain.
Voltage-gated sodium channels, such as Nav1.7, Nav1.8, and Nav1.9, play a pivotal role in nociception – the body’s way of sensing pain. Under physiological conditions, these channels contribute to the rapid transmission of pain signals following injury. However, in chronic pain, pathophysiological changes occur, including the overexpression or mutation of these channels, leading to conditions like erythromelalgia (a gain-of-function Nav1.7 mutation) or congenital insensitivity to pain (a loss-of-function Nav1.7 mutation). Similarly, TRP (Transient Receptor Potential) channels, notably TRPV1, are essential for detecting noxious heat and inflammatory pain. Their sustained activation and hyperactivity can shift a transient pain response into a chronic condition, perpetuating ongoing pain signals even in the absence of an external stimulus.
From physiological to pathophysiological pain
Understanding the transition from physiological to pathophysiological pain is not just of academic interest; it has profound clinical implications. By precisely targeting the specific ion channels involved in chronic pain, novel therapeutic strategies can be developed to interrupt these maladaptive processes. Such approaches have the potential to provide more effective pain relief while reducing the reliance on opioids and minimizing the risks associated with their use.
Developing ion channel modulators for treating chronic pain
Recent advances in neurobiology and pharmacology have led to the development of ion channel modulators that offer new hope for treating chronic pain. These innovative therapies target the root causes of chronic pain, addressing the underlying pathophysiological mechanisms rather than merely masking symptoms. This shift towards more precise and effective interventions marks a significant step forward in pain management, with the promise of improving the quality of life for millions of people suffering from chronic pain conditions such as neuropathic pain, migraines, and cancer-related pain.
Advancing pain research using automated patch clamping
Sophion’s automated patch clamp platforms are advancing pain research further and faster. A selection of recent, groundbreaking advances in the field are provided below, helping you navigate this rapidly developing area of pain research:
Prof. Stephen Waxman’s lab at Yale University have been at the forefront of pain research for decades. The lab’s latest publications provide methods and applications for acute isolation, purification, and ion channel recordings from nociceptive dorsal root ganglion (DRG) neurons:
Accurate, translatable, and relevant modelling of sensory nociceptive neuronal pathways will be key to developing our understanding of the underlying causes of chronic pain. In Kalia et al., a collaboration between the labs of Prof. Angelika Lampert, Prof. Irina Vetter, Prof. Ted Price and working with Anatomic Inc. and Sophion evaluated two induced pluripotent stem cell (iPSC) sensory neuron differentiation protocols:
Members of the voltage-gated sodium channel (VGSC) family are key instigators and drivers of pain signalling: the following link gives a round-up of recent developments in Nav ion channel physiology, pharmacology, and drug discovery, with a number of programmes targeting the Nav1.8 ion channel:
As we continue to explore the complex role of ion channels in the pain pathway, the future of pain management looks increasingly promising. Ongoing research in this field is vital, with the potential to revolutionize the way chronic pain is understood and treated.