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.
