Peripheral and Central Inflammation Caused by Neurogenic and Immune Systems and Anti- Inflammatory Drugs

General interrelationships between peripheral inflammation and hyperalgesia are discussed, citing previous reports. Neuroinflammatory substances and their intracellular mediators are briefly introduced. Algogenic substances (chemicals and natural products), their receptors, and anti-inflammatory drugs interrupting receptors, channels, and intracellular messengers are particularly highlighted. TRP channels are expressed on almost every tissue and cell type and conduct important regulation in the diverse cell functions. Allergic reactions are associated with thermosensing TRP channels (TRPV, TRPA, and TRPM). TRP channels are also expressed in immune cells and are therefore closely correlated with itching and inflammation. Nine thermosensing channels are the focus in allergies under normal and pathophysiological conditions. Although it is known that a proinflammatory cytokine (interleukin-1β: IL-1β) released from spinal microglia plays a crucial role in the induction and maintenance of acute and chronic pain states, the cellular basis of this action remains to be elucidated. The action of IL-β on synaptic transmission in spinal lamina II (substantia gelatinosa: SG) neurons has a pivotal role in the regulation of nociceptive transmission from the periphery. The experiment applied the whole-cell patchclamp technique to SG neurons in rat spinal cord slices and revealed that IL-1β pre- and postsynaptically enhanced glutamatergic spontaneous excitatory transmission while inhibiting spontaneous inhibitory transmission. These IL-1β actions could contribute to central sensitization and hyperalgesia in SG neurons.

Keywords: Antihyperalgesic drugs, central sensitization, glutamate receptors, IL- 1β, inflammatory mediators, Patch-clamp, peripheral sensitization, substantia gelatinosa neurons, thermosensing TRP channels.