We study the dynamic transcriptional and epigenetic changes in all cell types of the peripheral sensory system at single cell level, during progression of chronic pain, and reveal cell type-specific key molecular network interactions that regulate the transition from physiological to pathological nociception. Our final aim is to reverse the cellular state of affected cells in pain conditions and provide remission from unbearable acute pain and chronic pain.
Photo: n/aThe goal of the network is to stimulate scientific collaboration, interdisciplinary research, transmission of knowledge through seminars, lab rotation, both internal and external conferences and support promising projects with seed grants.
Pain is a warning and is therefore essential for preserving the functional integrity of our body.
Pain sensation begins peripherally by the activation in skin or deep tissue of nerve endings of a dozen subtypes of pain-sensing neurons, or nociceptors, whose cell bodies reside in the peripheral somatosensory ganglia (mostly the dorsal root ganglia, DRG, alongside the spinal cord). Centrally, distinct nociceptors project in specific lamina regions within the spinal cord where pain signal is locally processed before it is sent to upper brain centers for perception. When this normal pathway is damaged, one consequence can be a loss or reduction in pain, and also in other somatosensations (e.g. local numbness or hypoesthesia). On the other hand, however, injury to or diseases affecting the somatosensory nerves can also result in neuropathic pain (NP) without any obvious pain-inducing factor.
NP is usually chronic and includes dysesthesia or abnormal pain sensation which in some cases can be excruciating, but also allodynia (pain due to a stimulus that does not usually provoke pain, such as a light touch) and hyperalgesia (increased pain from a stimulus that usually provokes pain). Beside the pain itself, the presence of NP in patients has been consistently associated with reduced physical and emotional functioning (including anxiety and depression), and a general incapacitating effect that significantly influences the patients’ quality of life.
While a central origin of NP, resulting for instance from spinal cord injury or certain types of stroke, has been demonstrated, the majority of NP arises from lesions affecting peripheral nerves. Peripheral NP (or pNP) can occur following e.g., trauma, diabetic neuropathy, tumor or cytotoxic agents, nerve root compression and idiopathic painful peripheral neuropathy, and which have resulted in maladaptive plasticity in the somatosensory system being affected. These changes alter the electrical properties of the sensory nerves and shift the sensory pathways to a state of hyperexcitability.
A sequence of changes over time from the periphery can also affect the processing of sensory information centrally and lead to a loss of balance between excitatory and inhibitory neurotransmission in the spinal cord.
Therefore, initial, ectopic activity in the primary sensory nerves has a key role in the pathophysiology of neuropathic pain following peripheral nerve injury and study of cellular state changes is a central tenant towards development of new pain therapy.
Karolinska Institutet, Department of Neuroscience, SE-171 77 Stockholm
Karolinska Institutet, Biomedicum, D7
Solnavägen 9, SE-171 65 Solna
Tomtebodavägen 16, SE-171 65 Solna
