How the Mu Opioid Receptor Gene Controls Response to Painkilling Drugs (OPRM1)

Applied Cold

Cold exposure (e.g., with ice packs) is commonly used to reduce swelling and pain after traumatic injuries. It may also help reduce the pain and need for opioid medication after surgical procedures such as knee replacement and jaw or cruciate ligament reconstruction [R, R, R, R, R, R, R, R].

According to some preliminary research, intermittent swimming in cold water may stimulate pain-relief mechanisms that are mediated by our opioid system [R].

Exposure to cold – such as by taking cold showers or ice baths – has also been reported to increase levels of the “heat shock inducible factor”, a protein that stimulates mu and delta opioid receptors, according to two animal studies in rats [R, R].

Cold exposure appears to activate the opioid pain-relief system, which may be why ice packs reduce the need for opioid medication after surgery.

Acupuncture

Acupuncture is a form of alternative treatment developed by practitioners of Traditional Chinese Medicine. During acupuncture, thin metal needles are inserted at acupuncture points, or acupoints [R, R].

Stimulation of acupoints is believed to release endorphins and natural opioids in the body, thus reducing the perception of pain. In addition, it also reduces stress and tension [R].

The use of acupuncture to manage pain is highly controversial, but some researchers who study it believe that the body’s innate opioid system may play some role in its potential effects. Even if acupuncture’s effects are based solely on the psychological “placebo effect,” this effect could still involve the opioid system [R].

Additional research is required to investigate whether acupuncture works and how it affects the opioid system.

Acupressure

Acupressure is a form of Traditional Chinese Medicine similar to acupuncture, except that it involves the use of applied pressure in place of needles. Pressure is applied using the hands, thumbs, fingers, or devices to specific places (called acupoints) on the body. In a trial of 31 cancer patients, acupressure reduced the need for opioids by up to 44% [R].

Acupuncture and acupressure may stimulate the release of natural opioids like endorphins, reducing the perception of pain.

Positive Social Contact

Oxytocin (not to be confused with oxycodone!) is a neurotransmitter hormone that has long been associated with social and emotional bonding. Some people refer to oxytocin as the “love hormone” because it is believed to facilitate trust and attachment between individuals [R].

Although the mechanisms of oxytocin are quite complex, some researchers believe that at least part of its effects may be due to the stimulation of mu- and kappa-opioid receptors throughout the brain. These receptors may be responsible for oxytocin’s purported pain-killing (analgesic) effects [R, R].

Some research even suggests that oxytocin could be used as a replacement or a combination painkiller when opioids are inappropriate or insufficient [R].

To naturally boost oxytocin release, seek out positive social contact with people you love and trust. The best way to increase oxytocin release is through skin to skin contact [R].

Massage is also a good way to increase oxytocin. In a study of 95 adults, blood oxytocin increased after only 15 minutes of upper back massage. Likewise, a 10-minute foot massage increased blood oxytocin in 40 adult men. In this second study, participants’ oxytocin levels increased more dramatically when the massage was delivered by hand rather than by machine [R].

Positive social interaction and skin-to-skin contact stimulate the release of oxytocin, which may reduce pain through the opioid system.

Spicy Food

Capsaicin, the chemical that makes cayenne and chili taste spicy, increases endorphin release and activates opioid receptors in rats. Some people report feeling an endorphin rush-like “high” after eating very spicy food, but there is little research on this phenomenon [R, R].

There are multiple mechanisms by which capsaicin counter-intuitively reduces pain sensitivity. In brain cells, capsaicin activates the TRPV1 receptor. Although this protein triggers inflammatory pain, its repeated stimulation makes brain cells insensitive to pain perception. Capsaicin also seems to reduce the levels of substance P, which is involved in pain transmission, in the spinal cord [R, R].

Consuming capsaicin in spicy food may trigger the release of endorphins, which bind to opioid receptors. Capsaicin also has other pain-killing mechanisms.

Magnesium

In 60 patients who had just had surgery, magnesium amplified the analgesic effect of low-dose morphine in conditions of sustained pain. This early clinical trial confirmed the results of earlier rat studies. In each of these cases, however, magnesium did not itself activate the opioid receptors or release endorphins; rather, it potentiated the effect of another compound that did [R, R].

It is important to make sure you get enough dietary magnesium to allow opioids and opioid receptors to interact effectively. The best sources of magnesium are nuts, leafy greens, and whole grains [R].

Magnesium may be required for opioid receptor signalling. It is important to make sure you get sufficient magnesium through diet or, in some cases, supplements.