Pain 'helps body repair heart attacks'

“Stop being a wimp! Pain IS good for you,” reports the Daily Mail today. The paper goes on to say that pain plays “a crucial role in keeping us alive”.

The coverage is based on the results of a study performed in mice, with some preliminary experiments performed in humans. The study explored the effects of “substance P”, which is a chemical released by nerves in response to injury, or chemical or heat pain. The researchers looked at whether “substance P” played a role in tissue healing after a temporary block of blood flow. Blocking blood flow was used to mimic a blood clot or heart attack.

The study found that levels of substance P were increased after a temporary block of blood flow, causing bone marrow to release cells that are sensitive to substance P. These cells can potentially promote tissue healing and the formation of new blood vessels. This response was impaired if the mice were given morphine. Preliminary experiments in humans suggest that the process is likely to be similar.

This interesting study suggests that the pain response is important in the repair process, and that blocking it could be harmful. The researchers suggest that these findings might lead to new treatments, and that drugs that are compatible with both pain relief and with repair may need to be developed for people with cardiovascular problems, including having heart attacks.

However, despite the headlines, this study did not investigate whether pain relief hindered heart attack recovery or worsened outcomes in humans. Instead, the authors suggest that their experimental results could explain the findings of earlier research, which found that a painkiller (morphine) was associated with higher mortality in patients with acute coronary syndrome (a range of conditions including heart attack and unstable angina).

Where did the story come from?

The study was carried out by researchers from the University of Bristol and University College London; and the IRCCS MultiMedica, University of Udine and the University of Ferrara, Italy. It was funded by the European Union and the British Heart Foundation. The study was published in the peer-reviewed medical journal Circulation.

While The Daily Telegraph, The Guardian and the Daily Mail explained the research well, their headlines were exaggerated, as heart attack recovery and survival were not investigated in the study. The researchers state that their results may explain the findings of the CRUSADE Quality Improvement Initiative, which found that morphine was associated with higher mortality in patients with acute coronary syndrome.

What kind of research was this?

This was an animal-based study, with some preliminary experiments performed in humans. It aimed to determine whether substance P, a peptide released by sense nerves in response to injury or thermal or chemical painful stimulation, could play a role in tissue healing after a temporary block of blood flow.

This was the ideal study design to answer this question. However, it is not the ideal study design to determine whether pain relief hinders heart attack recovery or worsens outcomes.

What did the research involve?

The researchers initially conducted experiments in mice. They first investigated whether pain sense nerves were present in mouse bone marrow. They also looked at whether mouse bone marrow cells responded to substance P. They further examined the effects of substance P on mouse bone marrow cells in the laboratory.

The researchers then:

• temporarily blocked blood supply to a limb (to mimic a blood clot) in mice
• temporarily blocked blood supply to the coronary artery (to mimic a heart attack) in mice

They examined the effect of these two interventions on levels of substance P and the effect on bone marrow cells, and whether the response changed if the mice were given morphine. The researchers looked at the effect of the bone marrow cells on healing.

Finally, the researchers looked at whether the results were similar in humans. They investigated:

• whether human bone marrow cells responded in a similar way to substance P
• whether substance P levels changed after a heart attack in humans
• whether cells that are sensitive to substance P could promote healing in humans

What were the basic results?

The researchers found pain sense nerves in mouse bone marrow. They also found that mouse bone marrow “progenitor cells” (a type of cell that can change into a number of cell types) responded to substance P. The researchers found that blocking blood flow increased the levels of substance P in the circulating blood, and caused cells that are sensitive to substance P to be released from the bone marrow. In mice given morphine, both of these effects were reduced - substance P wasn’t released and cells were not released from the bone marrow. The researchers found that the cells sensitive to substance P were important for healing and blood vessel formation.

Human progenitor cells in bone marrow were also found to express receptors to substance P. The researchers also found that substance P levels were increased in patients who had had a heart attack. Human cells that are sensitive to substance P were able to promote blood vessel formation in the laboratory.

How did the researchers interpret the results?

The researchers conclude that their data show that substance P has an important role in blood vessel formation involved in healing. They state that this study could lead to further investigation into the role of pain signalling in progenitor cell mobilisation, and that this, in turn, could lead to the development of drugs that are compatible with pain relief and repair of the heart and circulatory system.

Conclusion

This animal-based study found that levels of “substance P” (a peptide released by sense nerves in response to injury or thermal or chemical painful stimulation) were increased after a temporary block of blood flow. They found that this caused cells that are sensitive to substance P to be released from the bone marrow. These cells have the potential to encourage tissue to heal and new blood vessels to form. The study found that this response was impaired if the mice were given morphine. Preliminary experiments in humans showed that the mechanism is likely to be similar.

This interesting study suggests that the pain response is important in the body’s repair process, and that blocking it could be harmful. The researchers suggest that these findings could potentially lead to new treatments. They also suggest that drugs that are compatible with both pain relief and with repair may need to be developed to treat people with cardiovascular problems, for example those having a heart attack.

Despite the headlines, this study did not investigate whether pain relief hindered heart attack recovery or worsened outcomes in humans. Instead, the authors suggest that their experimental results could explain the findings of earlier research, which found that morphine was associated with higher mortality in patients with acute coronary syndrome.