Opioids: pain memory erased

5. March 2012

A recent study shows that it is possible that, using short-term high-dose opioid administration, pain memory can be eliminated. Is this the future for patients with chronic pain? Clinical studies will show.

Different people feel pain differently. Birth pains, for example, are for some women a good experience, for others it is unbearable without painkiller. But no matter how the woman feels these pains, they are gone relatively quickly and soon forgotten. Quite different is the situation for people who suffer from chronic pain.

Pain memory – a flaw in the system?

Acute pain performs a useful and potentially life-sustaining function: it serves as a warning signal and alerts the body to injury or damage, from the outside or inside. This is not true for chronic pain. If pain receptors, so-called nociceptors, are constantly irritated by an acute pain event, a continuous signal is transmitted to the neurons of the peripheral nervous system. Over time, the constant firing of neurons leads to cellular changes at the synapses. Via so-called synaptic potentiation, a “memory lane” is created, which develops into a type of memory of pain in the spinal cord. The pain can remain as a chronic pain, even when the cause of the acute pain response itself is no longer present. Chronic pain is also thought of as being involved if the individual pain sensation clearly increases relative to the pain intensity which is objectively expected.

By definition, chronic pain lasts at least six months and hinders patients physically, psycho-cognitively and socially. The prevalence of chronic pain is difficult to determine accurately. Depending on the study and definition, in Germany it comprises between six and seventeen %.

Goodbye to pain memory – animal studies show: it is possible

Pain researchers at the Medical University of Vienna and the University Medical Center Mannheim have now succeeded in animal experiments using rats in extinguishing the memory of pain permanently. They achieved this with high-dose administration of opioids (Remifentanil, 450μg/kg/hour). Remifentanil is a potent opioid with rapid onset and a short duration of action. It possesses analgesic and sedative properties and is therefore used in surgery and in intensive care. Until now it was unknown that by using opioids the cause of pain can also be removed. In laboratory animals, pain-carrying neurofibres were excited under influence of deep anesthesia and the memory formation in the spinal cord was recorded. Short-term therapy with high-dose Remifentanil induced changes at the synapses, which were able to clear the cellular memory traces in the spinal cord. Studies involving chronic pain patients are already in the pipeline at the Medical University of Vienna. If the potential of this method can also be confirmed there, this might mean a paradigm shift in the treatment of pain: it would be possible to treat pain not only symptomatically, but to eliminate the cause permanently.

In the experiments within the study, pain-sensitive C-fibres were excited for short periods using electrical stimuli or capsaicin. In this way, a pain memory was generated. Here synaptic plasticity was brought about, but whether pain memory generated in this way is comparable to the situation in patients with chronic pain, sometimes developed over months or years, is unclear. Dr. Justus Benrath of the University Medical Center Mannheim, and co-author of the study, says however: “Pain memory is pain memory, it’s all the same no matter how it arises”. Therefore he has hope that the results can be extrapolated to humans.

Even if the method can successfully clear the memory of pain in humans, it remains to be seen whether there are adverse effects in the treatment. Even if with short-term administration the possibility of addiction – something always present with opioids – is low, it still first has to be ensured that the treatment itself actually leads to lasting effects.

Chronic pain is difficult to treat

Until now, the treatment of chronic pain has always been very difficult. For 13 to 51% of those patients affected, pain relief is inadequate, although different modes of treatment are used: conservative methods such as physical therapy, psychotherapy, or various methods of alternative medicine are important mainstays of therapy. In addition, treatment with drugs is normally added (paracetamol, anti-inflammatory drugs, codeine, morphine etc.). If these methods do not bring the desired effect, or side effects of the drug hinder effective treatment, neurostimulation or intrathecal drug infusions may be useful. As a final option their exists an operation, whereby an attempt is made, by means of creating a nerve blockage, to obstruct the transmission of pain signals to the brain. However, this is only useful if the cause of the pain is surgically remediable – that is to say, it is a consequence of “tangible” organic changes.

Pain memory is even more difficult to remove. Depending on the type and origin of the pain, beside the above-mentioned methods psychological treatments, such as stress and pain management training, or hypnotherapy, come into the picture. In so-called “relearning”, the attempt is made to overwrite pain memory via positive new experiences. To this end, the patient undergoing pain therapy has to expose himself or herself to genuinely painful situations. Because of the absence of pain which was present in the previously painful movement, the patient then – so to speak – reacts with positive surprise. If this positive experience can be repeated often enough, the basis for the elimination of pain memory is laid.

Prevention is better than cure

Experts now agree that many chronic pain conditions could be avoided if acute pain were treated as quickly and effectively and possible. The previous assumption was that “a little pain can’t hurt”; the situation is viewed differently today. In order to avoid the emergence of pain memory and the process of its chronic fixing, from the very beginning nowadays a comprehensive medical history of the pain is constructed and an individual optimisation of the treatment follows. The longer a pain exists, the more difficult and lengthy is the path to freedom from that pain. In some cases, only mere pain reduction is possible. The old saying “prevention is better than cure” is thus particularly true in pain management.

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