Skip to 0 minutes and 7 seconds In this short video, we will look at the transmission of a nerve impulse, such as pain, and how opioids affect this process. Opioid receptors are distributed throughout the nervous system. Of the three clinically significant type of opioid receptors– mu, delta, and kappa– the mu receptor is the principal mediator of analgesia and other related effects. Let’s look at the action potential. A nerve impulse is transmitted when the relative intra and extracellular charge across the axon membrane changes. This occurs when voltage gated ion channels allow sodium and potassium ions to cross the cell membrane. An incoming positive charge causes the sodium gate to open in this part of the axon.
Skip to 0 minutes and 54 seconds Sodium ions then move into the axon down their concentration gradient from high to low concentration. This reverses the resting membrane potential and is known as the action potential. The sodium gate then closes. There is a delay before the potassium gate opens. And when it does, potassium ions move down their concentration gradient and exit the axon. The potassium channel then closes. Sufficient net positive charge is left behind to open the adjacent sodium channel and set up a new action potential in the next section of the axon. It can only move in this direction because the proceeding voltage gated ion channels remain closed. Now, let’s look at opioid receptor binding. Opioid receptors are bound to the neuron cell membrane.
Skip to 1 minute and 47 seconds They are coupled to G proteins, which are activated when an opioid molecule binds to the receptor. The activated subunits then interact with other proteins of the cell. So how does this affect neurotransmission? When the incoming action potential reaches the presynaptic bulb, the intracellular positive charge rises. This causes voltage gated calcium ion channels in the presynaptic membrane to open, allowing calcium ions to flow in. In response to increased intracellular calcium concentration, neurotransmitter-containing vesicles migrate to and fuse with the presynaptic membrane. Neurotransmitter molecules are then released into the synaptic cleft. When the neurotransmitter molecule binds to receptors on the postsynaptic membrane, ion channels are activated to open, allowing positively charged ions to flow in.
Skip to 2 minutes and 43 seconds The increase in positive charge within the neuron is called depolarization. It causes poor synaptic voltage gated channels to open, allowing more positive ions to flow in and a new outgoing action potential is set up. Neurotransmitters are then released from their receptors and metabolised. So where do opioids come in? Opioids inhibit the action potential by acting at both presynaptic and postsynaptic terminals. In presynaptic inhibition, opioid molecules bind to receptors on the presynaptic membrane. This causes G protein activation and the release of the G beta gamma subunit. This interacts with nearby voltage gated calcium channels, preventing them opening and inhibiting neurotransmitter release.
Skip to 3 minutes and 38 seconds Opioids inhibit postsynaptic transmission by binding to opioid receptors on the postsynaptic membrane. Again, the G beta gamma subunit is activated. In this case, it causes ion channels to open, allowing positively charged potassium ions to exit the neuron. This means that even if neurotransmitters are released and depolarization has occurred, any action potential is negated by the loss of positive ions from the postsynaptic membrane.
Role of opioids in pain transmission
To fully appreciate the role of opioids in pain management, it helps to understand how they work on at a cellular level to disrupt pain signalling.
In this video animation Dr Victoria Hewitt explains the transmission of a nerve impulses such as pain and how opioids affect this process.
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