Elsevier

Environmental Research

Volume 188, September 2020, 109769
Environmental Research

Can wastewater analysis be used as a tool to assess the burden of pain treatment within a population?

https://doi.org/10.1016/j.envres.2020.109769Get rights and content

Highlights

  • Wastewater-based epidemiology shows promise for evaluating the prevalence of pain treatment in a population.

  • Pain indices estimated by the measurement of analgesic drugs in wastewater.

  • Indices for mild to moderate pain can be calculated via nonsteroidal anti-inflammatory drugs (NSAIDs) defined daily doses (DDD).

  • A strong to severe pain index can be calculated via opioid DDDs or morphine equivalents.

Abstract

Pain is a global health priority that is challenging to asses. Here we propose a new approach to estimating the burden of pain treatment in a population using wastewater-based epidemiology (WBE). WBE is able to quantify multiple pharmaceutical compounds in order to estimate consumption by a population. Wastewater samples collected from areas representing whole communities can be analysed to estimate the consumption of drugs used to treat pain, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids. The collection and analysis of wastewater can be conducted systematically to estimate the total consumption of NSAIDs and/or opioids in the population of a catchment area and to compare changes over time within the catchment or between different catchment populations. Consumption estimates can be combined by standardising the mass consumed to Defined Daily Doses (DDD) or morphine equivalents in order to assess, the population burden of pain treatment from mild to moderate (for NSAIDs) and for strong and severe pain (for opioids). We propose this method could be used to evaluate the total pain treatment burden between locations and over time. While this concept shows promise, future studies should evaluate the applicability as a tool to measure the burden of pain receiving treatment in a community.

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.

References (126)

  • R. Bruno et al.

    Association between purity of drug seizures and illicit drug loads measured in wastewater in a South East Queensland catchment over a six year period

    Sci. Total Environ.

    (2018)
  • C. Chen et al.

    Towards finding a population biomarker for wastewater epidemiology studies

    Sci. Total Environ.

    (2014)
  • P.M. Choi et al.

    Wastewater-based epidemiology biomarkers: past, present and future

    Trac. Trends Anal. Chem.

    (2018)
  • C.G. Daughton

    Monitoring wastewater for assessing community health: sewage Chemical-Information Mining (SCIM)

    Sci. Total Environ.

    (2018)
  • K. Diamanti et al.

    Wide-scope target and suspect screening methodologies to investigate the occurrence of new psychoactive substances in influent wastewater from Athens

    Sci. Total Environ.

    (2019)
  • P. Du et al.

    Estimating heroin abuse in major Chinese cities through wastewater-based epidemiology

    Sci. Total Environ.

    (2017)
  • K.C. Duggan et al.

    Molecular basis for cyclooxygenase inhibition by the non-steroidal anti-inflammatory drug naproxen

    J. Biol. Chem.

    (2010)
  • R.H. Dworkin et al.

    Core outcome measures for chronic pain clinical trials: IMMPACT recommendations

    Pain

    (2005)
  • E. Emke et al.

    Wastewater-based epidemiology generated forensic information: amphetamine synthesis waste and its impact on a small sewage treatment plant

    Forensic Sci. Int.

    (2018)
  • W.P. Farquhar-Smith

    Anatomy, physiology and pharmacology of pain

    Anaesth. Intensive Care Med.

    (2008)
  • K.S. Foppe et al.

    Estimation of the consumption of illicit drugs during special events in two communities in Western Kentucky, USA using sewage epidemiology

    Sci. Total Environ.

    (2018)
  • D.E. Furst

    Meloxicam: selective COX-2 inhibition in clinical practice

    Semin. Arthritis Rheum.

    (1997)
  • J. Gao et al.

    Systematic evaluation of biomarker stability in pilot scale sewer pipes

    Water Res.

    (2019)
  • D.J. Gaskin et al.

    The economic costs of pain in the United States

    J. Pain

    (2012)
  • E. Gracia-Lor et al.

    Refining correction factors for back-calculation of illicit drug use

    Sci. Total Environ.

    (2016)
  • E. Gracia-Lor et al.

    Measuring biomarkers in wastewater as a new source of epidemiological information: current state and future perspectives

    Environ. Int.

    (2017)
  • R. Gurke et al.

    Development of a SPE-HPLC–MS/MS method for the determination of most prescribed pharmaceuticals and related metabolites in urban sewage samples

    J. Chromatogr. B

    (2015)
  • A.J. Gushgari et al.

    Long-term tracking of opioid consumption in two United States cities using wastewater-based epidemiology approach

    Water Res.

    (2019)
  • A.J. Gushgari et al.

    Tracking narcotics consumption at a Southwestern US university campus by wastewater-based epidemiology

    J. Hazard Mater.

    (2018)
  • A. Ho et al.

    Chapter nine - global chronic pain: public and population health responses

  • M.P. Jensen et al.

    Comparative reliability and validity of chronic pain intensity measures

    Pain

    (1999)
  • A. Kankaanpää et al.

    Current trends in Finnish drug abuse: wastewater based epidemiology combined with other national indicators

    Sci. Total Environ.

    (2016)
  • S. Karolak et al.

    Estimation of illicit drugs consumption by wastewater analysis in Paris area (France)

    Forensic Sci. Int.

    (2010)
  • B. Kasprzyk-Hordern et al.

    The removal of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs during wastewater treatment and its impact on the quality of receiving waters

    Water Res.

    (2009)
  • K.Y. Kim et al.

    The first application of wastewater-based drug epidemiology in five South Korean cities

    Sci. Total Environ.

    (2015)
  • K. Kołecka et al.

    Spatial distribution of pharmaceuticals in conventional wastewater treatment plant with Sludge Treatment Reed Beds technology

    Sci. Total Environ.

    (2019)
  • C.I. Kosma et al.

    Investigation of PPCPs in wastewater treatment plants in Greece: occurrence, removal and environmental risk assessment

    Sci. Total Environ.

    (2014)
  • I. Krizman et al.

    Wastewater-based assessment of regional and temporal consumption patterns of illicit drugs and therapeutic opioids in Croatia

    Sci. Total Environ.

    (2016)
  • I. Krizman-Matasic et al.

    Long-term monitoring of drug consumption patterns in a large-sized European city using wastewater-based epidemiology: comparison of two sampling schemes for the assessment of multiannual trends

    Sci. Total Environ.

    (2019)
  • R. Kumar et al.

    Assessment of drugs of abuse in a wastewater treatment plant with parallel secondary wastewater treatment train

    Sci. Total Environ.

    (2019)
  • F.Y. Lai et al.

    Refining the estimation of illicit drug consumptions from wastewater analysis: Co-analysis of prescription pharmaceuticals and uncertainty assessment

    Water Res.

    (2011)
  • Z. Li et al.

    Pregabalin is a potent and selective ligand for α2δ-1 and α2δ-2 calcium channel subunits

    Eur. J. Pharmacol.

    (2011)
  • T. Mackuľak et al.

    Music festivals and drugs: wastewater analysis

    Sci. Total Environ.

    (2019)
  • N. Mastroianni et al.

    Five-year monitoring of 19 illicit and legal substances of abuse at the inlet of a wastewater treatment plant in Barcelona (NE Spain) and estimation of drug consumption patterns and trends

    Sci. Total Environ.

    (2017)
  • S. Mercan et al.

    Wastewater-based monitoring of illicit drug consumption in Istanbul: preliminary results from two districts

    Sci. Total Environ.

    (2019)
  • R.L. Nahin

    Estimates of pain prevalence and severity in adults: United States, 2012

    J. Pain

    (2015)
  • H.T. Nguyen et al.

    Assessment of drugs and personal care products biomarkers in the influent and effluent of two wastewater treatment plants in Ho Chi Minh City, Vietnam

    Sci. Total Environ.

    (2018)
  • J.W. O'Brien et al.

    A National Wastewater Monitoring Program for a better understanding of public health: a case study using the Australian Census

    Environ. Int.

    (2019)
  • T.S. Oliveira et al.

    Characterization of Pharmaceuticals and Personal Care products in hospital effluent and waste water influent/effluent by direct-injection LC-MS-MS

    Sci. Total Environ.

    (2015)
  • G. Olveira et al.

    Usefulness of the daily defined dose method to estimate trends in the consumption, costs and prevalence of the use of home enteral nutrition

    Clin. Nutr.

    (2009)
  • Cited by (0)

    View full text