Can wastewater analysis be used as a tool to assess the burden of pain treatment within a population?
Graphical abstract
Introduction
The growing global burden of pain is associated with many diseases. Pain has no boundary, its effects do not discriminate between age groups, gender, race or geographic regions (Ho and Nair, 2018). It has been reported that 1 in 5 adults will experience some level of pain each year (Goldberg and McGee, 2011). While pain is not listed as a cause in the burden of disease, each the top 8 chronic non-communicable diseases (NCDs) e.g. back and neck pain, are strongly associated with the symptoms of chronic pain (Jackson et al., 2016). The World Health Organization (WHO) predicts that chronic pain will be a common form of co-morbidity with the top four causes of the global burden of disease by 2030 (Van Hecke et al., 2013).
High-income countries face an increased burden of chronic pain, with studies showing for example 9% of adults are affected in Singapore (Yeo and Tay, 2009), 11% in the United States of America (USA), 19% in Canada (Nahin, 2015; Schopflocher et al., 2011) and 30% in Norway (Breivik et al., 2006). The extent of the chronic pain problem poses a significant economic burden for both patients and health services. In the USA it is estimated that chronic pain cost the economy between US $299 to $335 billion a year, more than heart disease ($309 billion), cancer ($243 billion) and diabetes ($188 billion) (Gaskin and Richard, 2012). A 2018 study in Australia reported the financial cost of chronic pain to the country was AUD $73.2 billion (Australia March 2019).
The experience of pain is subjective and influenced by mood and psychological state, early life experiences, medical conditions and the social environment (Shankland Ii, 2011), all of which complicate the measurement of an individual's pain. Nonetheless, assessment is necessary for medical treatment, diagnosis and monitoring disease states. Individual pain assessments generally use visual analogue and verbal rating scales, such as The McGill pain questionnaire. Others evaluate behavioural responses and physiological indicators (Relland et al., 2019). Recently, electromyography and microneurography have been used as advanced tools for pain measurement (Chu et al., 2017). All the above methods have both positive and negative features but are limited to measuring the pain of individuals. To date, a key challenge is assessing the prevalence and spatio-temporal distribution of pain in a community or population.
Opioids and non-opioids have for a long-time been used for pain medication (Haroutiunian et al., 2010; Schnitzer, 1998). Following the use of opioids or non-opioids for pain relief, the body metabolises them and excretes the parent compounds and/or metabolites via urine, finally ending in the sewer network. Back calculation of metabolite/biomarker load from influent wastewater can be used to estimate the population's drug consumption and provide estimates of its analgesic drug loads. This method is known as wastewater-based epidemiology (WBE) (Daughton, 2018; Zuccato et al., 2008). It involves the systematic collection of samples of raw wastewater from inflows to wastewater treatment plants (WWTPs) and instrumental analysis of concentrations of target biomarkers in the samples. WBE can estimate the mg consumed per day per 1000 inhabitants by normalizing results to the daily flow of wastewater, the catchment population, and pharmacokinetics (urinary excretion). These units can be compared between locations and over time. The overall consumption rates provide insights into community health status and provides valuable epidemiological information on the consumption of different drugs (Daughton, 2001, 2018; Gracia-Lor et al., 2017; Zuccato et al., 2008). WBE has been successfully employed to measure the consumption of several substance classes and monitor public health (Ahmed et al., 2020; Tscharke et al., 2016; Zheng et al., 2017).
This article suggests a new method of measuring the total population burden of treatment pain. It proposes to quantify and profile of analgesic drugs in wastewater followed by normalisation of the relative drug potency to convert mass loads to estimate daily doses or morphine equivalents. It provides the theoretical basis for using wastewater-based pain indices to evaluate the pain burden of communities. Herein we suggest two pain indices: one related to mild to moderate pain based on NSAID using nonsteroidal anti-inflammatory drug consumption profiles; and one for strong to severe pain based on the consumption profile of opioids. Detailed steps for measuring pain by WBE at the population-level are also discussed.
Section snippets
Definition of pain
Pain is a complex sensory and emotional experience associated with tissue damage (Farquhar-Smith, 2008). It signals to protect the body from danger due to shock, suffering, trauma and injury. Pain can arise in a particular part of the body and it can be differentiated qualitatively by the sensations it produces (e.g. burning, stinging, pricking, throbbing, dull or aching). The peripheral nervous system signals tissue damage via a process called nociception in which a stimuli, such as injury,
Expected outcomes
The incidence of pain and its substantial comorbidities and its further connection with numerous social and economic factors provide ample justification for treating pain as a public health priority. However, measurement of the population burden of pain treatment is generally lacking. Because pain is associated with medical costs and productivity losses such a method could also contribute to assessments of the economic impact of pain from a societal perspective. The correlation between the
Limitations
There are several limitations that need to be considered when evaluating this approach. Wastewater analysis cannot distinguish between different routes of drug administration e.g. oral, intramuscular or intravenous. Because pain is multifactorial, a combination of NSAIDs and opioids may be used for the treatment of acute pain. Wastewater analysis cannot reveal when pain is not treated using pharmaceuticals (e.g. by physiotherapy, exercise or psychological approaches). In addition, some
Conclusion
As the global pain burden is increasing in different countries, there is a need for a suitable approach to measure the population's burden of pharmaceutically treated pain. This article presents an approach in which the burden of treated pain can be estimated using wastewater-based epidemiology. This method can be used to rank the pain burden in an area and to categorise pain levels within the population.
CRediT authorship contribution statement
Fahad Ahmed: Conceptualization, Writing - original draft, Writing - review & editing. Benjamin Tscharke: Writing - review & editing, Supervision. Jake W. O'Brien: Writing - review & editing, Supervision. Peter J. Cabot: Writing - review & editing. Wayne D. Hall: Writing - review & editing. Jochen F. Mueller: Writing - review & editing, Supervision. Kevin V. Thomas: Writing - review & editing, Supervision.
Declaration of competing interest
The authors have no conflict of interest to declare.
Acknowledgment
The Queensland Alliance for Environmental Health Sciences, The University of Queensland, gratefully acknowledges the financial support of the Queensland Department of Health. Fahad Ahmed is the recipient of The University of Queensland Research Training Scholarship and a QAEHS Research Higher Degree Top-Up Scholarship.
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