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Pain and its Association with Mortality

May 18, 2021
 
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Brianna Belton, PharmD. Candidate, Florida Agricultural & Mechanical University, College of Pharmacy and Pharmaceutical Sciences

Patients experiencing pain along with their diabetic polyneuropathy are at an increased risk of vascular events and mortality. 

Diabetic polyneuropathy (DPN) experienced by patients with type 2 diabetes mellitus results from damage to the nerves. Polyneuropathy refers to many or most of the nerves being affected. The type of nerves that are damaged and the severity of the damage determines the symptoms. The type of nerves that can be damaged are the motor, sensory, and autonomic nerves. This damage can be accompanied by pain and numbness, and loss of function of certain parts of the body, such as the heart and digestive system. Damage to motor neurons can result in muscle weakness. Damage to sensory neurons can result in loss of feeling; there is a reduced ability to feel vibrations, touch, temperature, and pain. Damage to autonomic nerves can result in the loss of function of the organs that regulate the activities done without conscious control, such as regulation of blood pressure, eating food, and heat intolerance.  

 

It is known that diabetic polyneuropathy is also associated with vascular events and mortality. Vascular events are conditions that affect the blood vessels and are common complications experienced in patients with diabetes. More severe vascular events can lead to amputations, disabilities, and death. What is unknown is the association between pain with DPN and the risk of vascular events and mortality, and what causes this pain. 

In a retrospective cohort study, 43,495 adult patients with type 2 diabetes were classified into three groups: no DPN, DPN plus pain, and DPN without pain. The primary outcomes were the number of vascular events and time to mortality. 13,910 patients (31.7%) had DPN. 9,104 had DPN plus pain (65.4%) while 4,806 had DPN, but without pain (34.6%). In the group without DPN, vascular events occurred in 4,538 (15.1%) of the patients. Vascular events occurred in 2,401 patients (26.4%) in the DPN plus pain group, and 1,006 (20.9%) occurred in the DPN without pain group.  

Adjustments were made in the DPN plus pain group for specific patient factors: demographics, socioeconomic characteristics, and comorbidities. After adjustment, comparing the DPN plus pain group to the group without DPN, the DPN plus pain group remained a significant predictor of several vascular events (Incidence Rate Ratio (IRR)=1.55, 95% CI 1.29-1.85) while the group without DPN was protective (IRR=0.70, 95% CI: 0.60-0.82). Comparing the DPN plus pain group to the DPN without pain group, the DPN plus pain group was also a significant predictor of mortality (HR=1.42, 95% CI 1.25-1.61).  

This study found a significant association between pain associated with DPN and an increased risk of vascular events and mortality. More studies are needed to evaluate why this association exists.  

Other studies have shown that pain can lead to many complications, even if the pain is not related to diabetic polyneuropathy. One study, in particular, is Relationship Between Postoperative Pain and Overall 30-Day Complications in a Broad Surgical Population: An Observational Study. This study was aimed to establish the relationship between postoperative pain and postoperative complications after 30 days. In the 1014 enrolled patients, 55% experienced moderate-to-severe pain on the first postoperative day and 34% experienced complications. Patients who rated their pain as unacceptable experienced even more complications. This study showed that higher postoperative pain scores and unacceptable pain were associated with more postoperative complications. Pain dramatically influences how well patients will respond to treatment and affects their overall health. 

These studies emphasize the importance of understanding and combatting existing pain. If patients go to their physicians with complaints of pain, it is vital to take it seriously. Even if patients are not reporting pain, specific measures should be taken to determine if the patient is experiencing any pain. These measures may help alleviate the pain that may be present, improve quality of life and prevent complications. 

Practice Pearls: 

  • Diabetic polyneuropathy is associated with an increased risk of vascular events and mortality. This study was aimed to determine the effect that pain associated with polyneuropathy has on vascular events and mortality. 
  • There is a significant association between diabetic polyneuropathy plus pain and an increased risk of vascular events and mortality. 
  • Now, it is vital to determine the risk factors for pain in diabetic polyneuropathy and reduce them. 
  • Patients experiencing pain, in general, can lead to more complications versus patients that are not experiencing pain. Alleviating pain can lead to better results and improve quality of life.  

 

Boekel, R. L., Warlé, M. C., Nielen, R. G., Vissers, K. C., Sande, R. V., Bronkhorst, E. M., . . . Steegers, M. A. (2019). Relationship Between Postoperative Pain and Overall 30-Day Complications in a Broad Surgical Population. Annals of Surgery, 269(5), 

Lapin, B. R., Pantalone, K. M., Milinovich, A., Morrison, S., Schuster, A., Boulos, F., . . . Thakore, N. J. (2020). Pain in Patients with Type 2 Diabetes-related Polyneuropathy is Associated with Vascular Events and Mortality. The Journal of Clinical End 

Peripheral Neuropathy Fact Sheet. (2018, August). Retrieved July 12, 2020, from https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Peripheral-Neuropathy-Fact-Sheet 

 

Brianna Belton, PharmD. Candidate, Florida Agricultural & Mechanical University, College of Pharmacy and Pharmaceutical Sciences