High calcium and neuropathy

The possible connection between calcium and pain

When considering calcium disturbances in sarcoidosis, it is useful to ask what roles calcium has in the body beyond its importance for bones. Could an increased calcium level, related to macrophage activity, be connected with pain?

Calcium is actively involved in nervous-system signalling and neurotransmission. Neurotransmission is the process by which signalling molecules called neurotransmitters are released from the axon terminal of one neuron and bind to receptors on another neuron.

Roles of calcium in nervous-system signalling include helping electrical signals travel along axons and triggering synaptic terminals to release neurotransmitters into synapses. Calcium is also involved in memory formation, metabolism and cell growth. Calcium ions are essential to many nervous-system functions, from neurotransmitter release to intracellular signal transduction.

Calcium ions play a key role in triggering transmitter release at neuromuscular junctions and from chromaffin granules in the adrenal medulla. They also regulate responses of the central nervous system to injury. Calcium entering injured cells can activate phospholipases, disturb mitochondrial electron transport and promote the release of free radicals.

The main role of calcium at the synapse is to link presynaptic depolarisation with transmitter release. Uncontrolled activation of ionotropic receptors can cause excessive calcium entry through the plasma membrane. Along with disturbances in synaptic activation and neuronal plasticity, this can activate calcium-dependent enzymes involved in the breakdown of proteins, phospholipids and nucleic acids.

Disturbed calcium levels may contribute to neurodegenerative disease. A reduced ability of neurons to maintain cellular energy and control reactive oxygen species (ROS) may affect calcium signalling during ageing and in neurodegenerative processes. After cerebral ischaemia, calcium dysregulation is considered one of the mechanisms that can contribute to neuronal cell death and brain injury. Failure to maintain calcium homeostasis may result from increased calcium entry and impaired removal of calcium through the plasma membrane.

The original article proposes that, in this context, there could be a causal relationship between sarcoidosis, neuropathy and painful joints. This is a hypothesis and not an established explanation for pain in every person with sarcoidosis. Persistent or worsening neuropathic pain, weakness or joint symptoms should be assessed by a healthcare professional.

Dino-Josip Ključarić

This page is educational and does not replace medical examination or individual treatment advice.