In populations with substance use disorders (SUD), there is a high prevalence of chronic pain with various underlying causes. Chronic pain can complicate the treatment of SUD and lead to poorer treatment outcomes. There is a need for a better understanding of the connections and interactions between chronic pain and substance use and dependence.

Further, there is a high prevalence of chronic pain among patients with post-traumatic stress disorder (PTSD). As there is an overlap between populations with SUD and PTSD, taking potentially traumatizing life-experiences and post-traumatic stress symptoms into account can provide a better understanding of chronic pain in populations with SUD.

The Nor-APT study is a cross-sectional study, recruiting from outpatient and inpatient substance use treatment centres connected to four hospitals. Participants complete a questionnaire about substance/medication use, pain and how pain affect function, stressful life events and post-traumatic stress symptoms. Patients can consent to self-reported data being linked to retrospective and prospective longitudinal data from national demographic and health registries.

The purpose of the study is to contribute to a better understanding and treatment of chronic pain among people with substance use disorders (SUD), and to contribute to the understanding of co-occurring substance use, chronic pain and post-traumatic stress symptoms.

The over-arching research aims are to:

I. Describe the prevalence and characteristics of pain for people in need of treatment for substance/medication use/dependence.

II. Describe how the pain affects physical and emotional functioning, and subjective quality of life.

III. Explore any connections between substance/medication use and pain, both what came first and any ways substance/medication use and pain affect each other.

IV. Explore the connection between chronic pain, potentially traumatizing life events and post-traumatic stress symptoms.

V. Explore how treatments received and how treatment affects outcomes.

In addition, we will explore whether participants' experiences can be categorized into typical trajectories for how substance use, chronic pain and stressful life events occur and develop over the life span.

INTRODUCTION

Chronic pain and substance use

The prevalence of chronic pain is high among persons with opioid dependence and alcohol dependence. According to a recent review, it is common for patients to use both opioids and alcohol, and this is seen especially in cases where the patient also experiences chronic pain. Nevertheless, alcohol use is often omitted from research on opioids and chronic pain. The review concludes that there is a great need for more knowledge about co-use of alcohol and opioids in people with chronic pain.

The high prevalence of chronic pain in populations with opioid or alcohol dependence could be related to comorbid physical illness and injuries, which is prevalent among opioid dependent patients. It is also possible that use of opioids or alcohol can contribute to pain sensitivity and worsening of pain over time.

There have been few studies focusing on chronic pain and dependence on other substances than opioids or alcohol. The prevalence of chronic pain among people with, for example, amphetamine dependence or cannabis dependence has received little attention, although cannabinoids are also used as prescription painkillers.

A study of the general population in the United States found a link between chronic pain and marijuana use, but could not discern whether the pain or marijuana use came first. In a small study, two out of five people using marijuana or cocaine reported using the substances as pain relief. Amphetamine is also a highly relevant substance when it comes to pain, as amphetamines can be analgesic, and can enhance the analgesic effect of opioids.

Chronic pain is associated with poorer treatment outcomes, however there is little knowledge about how co-occurring chronic pain and substance dependence develops over time. More knowledge about the mechanisms behind co-occurring chronic pain and dependence can contribute to better treatment options for patients, both when it comes to the treatment of pain and dependence.

Chronic pain and PTSD

Chronic pain and pain intensity have a documented association with post-traumatic stress disorder (PTSD) in the general population, but have not been much explored among people with dependence. A small study has found a higher prevalence of chronic pain among people with co-occurring substance dependence and PTSD, but the study was not large enough (n = 133) to distinguish between dependence on different types of substances. One study (n = 150) found a higher prevalence of PTSD among methadone patients with chronic pain.

Unfortunately, PTSD is a diagnosis that has historically been considered difficult to treat among people with substance use disorder. Therefore PTSD is undertreated for these patients.

The link between chronic pain and PTSD is not fully understood. In some cases, the pain may be caused by a physical injury in connection with the event that caused the PTSD. Beyond these cases, some theories focus on shared vulnerability, or that chronic pain and PTSD reinforce each other through excessive reactions to or misinterpretation of stress or pain stimuli. Other theories focus on the biological aspects, such as dysregulation of the nervous system or dysregulation of opioid receptors.

It is also possible that the PTSD symptoms associated with overactivation may drive the association between PTSD and pain. This makes it relevant to explore any potential interaction effects of PTSD symptoms and the use of sedative and stimulating substances/medications on the experience of pain.

A better understanding of the links between chronic pain, PTSD and dependence can mean a lot for better treatment of patients with comorbid substance dependence, PTSD and pain disorders.

METHODS

Design. Cross-sectional survey study, with linkage to retrospective and prospective registry data. The NOR-APT study employs a rarely utilized research design where survey data containing the patients' self-reported experiences are combined with high quality, nearly complete, longitudinal registry data from the first and second line health care services and the prescription database, as well as sociodemographic registries.

Data from the first registration of the patient in the registries can be linked to self-reported data through personal identification numbers retained by all residents, providing a complete history of treatments and diagnoses.

It is a multicentre study, with data collected from over 20 substance use treatment centres in the catchment areas for Akershus University Hospital, Oslo University Hospital, Vestfold Hospital Trust and Telemark Hospital in Norway.

Participants. The goal is to recruit 1 500 patients entering any form of substance use treatment at the 20+ collaborating inpatient and outpatient clinics.

Staff at the treatment centres are instructed to ask all patients. At the time-points where 500 and 1 000 questionnaires have been completed, the investigators will assess the distribution of participants according to their primary substance use problem/the substance they are in treatment for. If the distribution is skewed in a manner that may not give enough data about some sub-groups of substance users, the investigators may encourage staff at the treatment centres to continue with more selective recruitment of the patient groups that are underrepresented. For instance, many patients are treated for opioid or alcohol dependence, so this group may be recruited faster and more easily, while patients with a primary dependence to cannabis or amphetamines may be fewer and could require more time and effort to reach a sufficiently large sample size.

Materials. The questionnaire was developed based on the research questions, previous literature, and in collaboration with the clinicians that see the patient groups in their day to day practice at Akershus University Hospital and Oslo University Hospital. The questionnaire was piloted on 10 patients with different substance use patterns, where patients were asked to comment on the experience of filling in the questionnaire, the length and clarity of the questions, and give any other comments or suggestions. Further adjustments to the layout and wording of certain questions were made based on the results of the piloting.

To make the data-collection process as uniform as possible, a questionnaire guide for staff was made, with a standard text for introducing and explaining the questionnaire to patients, and with a walk-through of the questions with additional explanations, definitions and problem-solving for common issues when filling out the different type of questions. In the guide, other topics related to collecting survey-data were also addressed, such as concerns related to missing responses for data validity and how to balance the preference for complete answers with ensuring that all questions were answered on a completely voluntary basis.

An instructional 15 minute video for staff was made, with an explanation of the background and purpose of the study, as a measure to increase understanding and motivation for recruiting patients to the study.

Registry data: The Norwegian registries consist of high-quality data on for instance treatment episodes, diagnoses, prescribed medications and socioeconomic variables, with nearly complete data for all individuals in Norway.

Procedure. Each treatment centre has a study coordinator responsible for ensuring all staff has access to questionnaires, guides and the instructional video. The coordinators task is to inform staff and distributed the study material. The coordinator will also report on progress, issues and concerns to the central study coordinators throughout the data collection period.

Staff at the treatment centres are instructed to invite all patients (except those affected by the exclusion criteria) to participate. Patients will be informed that participation is voluntary and that declining to participate will not affect the treatment they receive, about the purpose of the study and how the information they give will be handled. The number of patients that decline participation will be logged, and if the patients consent to disclosing the information, the gender, age and which substance they are in treatment for/their primary substance problem, will also be logged for patients that decline participation.

Patients that agree to participate will complete the consent form and the questionnaire. If they wish to withdraw from the study at a later time, they can contact the treatment centre or the research group.

For participants who consent to linkage of questionnaire data with longitudinal registry data, linkage to retrospective registry data will be performed about a year after collection of questionnaire data has been completed, and linkage to prospective registry data will be done 5-6 years after the collection of questionnaire data have been completed. Linkages are performed by the Norwegian Institute of Public Health and Statistics Norway, based on the patients explicit consent and unique personal identification number.

Inclusion Criteria:

• Patient in substance use treatment at a treatment centre under Akershus University Hospital, Oslo University Hospital, Vestfold Hospital or Telemark Hospital.

Exclusion Criteria:

Staff considers the patient to be unable to give informed consent/valid responses on the questionnaire OR staff considers participation to be too stressful/burdensome to the patient. Staff are asked to take the following into consideration when making their assessment:

• Acute withdrawal
• Acute intoxication
• Serious mental health concerns
• Serious physical health concerns

Patients (ages 18 years - unlimited) in treatment for substance use disorders at outpatient and inpatient treatment centers connected to Akerhus University Hospital or Oslo University Hospital, Norway.