home
team
tour
tour
publication
teaching
student_lab

Department of Molecular Physiology

Our interests

Pain
Introduction

Pain cells (nociceptors) report to the brain sensory stimuli that are strong enough to cause tissue damage, such as excessive heat, mechanical stress, or chemical insult. Nociceptors thus help us to avoid injury and to maintain the integrity of the body. How do these sensory neurons detect noxious stimuli? How do they handle the sensory signal on the way from the skin to the spinal cord? We are interested to learn more about the regulation of excitability in pain cells, about the ion channels that conduct pain signals toward the central nervous system, and the synapse that transmits the signal to a spinal-cord neuron.

Nociceptors can be very long neurons. With their sensory endings in the skin, in joints or muscles, they can measure more than a meter up to their synaptic ending in dorsal horn of the spinal cord. The somata of most nociceptors are collected within the dorsal root ganglia, one of which lies at either side of each vertebra. Each soma is the origin of a bifurcated axon which projects to the sensory ending at the periphery and to the synaptic ending in the spinal cord. Aδ-fibers with thick, myelinated axons conduct rapid pain signals to the spinal cord, while C-fibers have thin, non-myelinated axons and mediate slow, persistant pain perception.

The sensory endings of nociceptors usually respond to very strong stimuli: temperatures in excess of 40 oC, acid solutions, cuts, bruises, etc. In contrast to subtle sensory stimuli like dim light or weak odors, such intense stimulation does not recquire amplifying mechanisms in the sensory cell. In pain cells, the stimulus usually acts directly on a transduction channel, opens it and causes depolarization and electrical excitation of the neuron. Various of these transduction channels have been identified. TRPV1 and TRPV2 channels are opened by painful heat, channels of the degenerin family (DEG) by mechanical stimulation, acid-sensing ion channels (ASICs) are gated by protons, and purinergic receptors (P2X3R) open when ATP escapes damaged cells and comes in contact with sensory endings of nociceptors. These transduction channels conduct the receptor current that triggers action potentials through a set of voltage-gated cation channels (red circle).

A particularly interesting aspect of nociceptor function is sensitization. Sensory endings in inflamed tissue display much enhanced sensitivity to stimulation so that ususally non-painful stimuli become painful (allodynia) and the perception of painful stimuli becomes more intense (hyperalgesia). This is probably caused by chemical modification (phosphorylation) of the transduction channels in sensory endings. Various inflammatory mediators like bradykinin and prostaglandins have been shown to cause sensitization in this way. Thus, the sensory endings of nociceptors are modulated and, through them, the perception of pain.

The synaptic ending of nociceptors is fascinating both for physiological and for pharmacological reasons. Nociceptors form synaptic contact with spinal-cord neurons within the dorsal horn this is the place, where the pain signal enters the central nervous system. The synaptic ending of a nociceptor is under the control of a system that is designed to suppress pain perception. Special interneurons in the dorsal horn can use endorphin or enkephalin as neurotransmitters to interrupt the transmission of the pain signal. This pain-blocking effect is mediated by morphin receptors, named after the pain-relieving component of opium, and acts by inhibiting presynaptic voltage-gated calcium channels. Opening of these channels is necessary for neurotransmitter release and synaptic transmission of the pain signal. The channels themselves are targets of omega-conotoxin, a neurotoxin from the venom of marine cone snails. The toxin is used in pain therapy - as a compound that disrupts the communication of pain signals to the brain.



Top

Back