Oxytocin in Chronic Neck and Shoulder Pain

Oxytocin (24 International Units) administered via nasal spray. Participants will self administer the intranasal spray under verbal instructions from the researcher. Participants will be instructed to keep the bottle in an upright position during the puffing. Before puffing commences, four pre-puffs will squirted from the spray bottle by the researcher to ensure normal distribution of each spray before use. The order of administration was always as follow: insert spray-head, exhale,  puff, inhale nasally. Administration will alternate between the nostrils after each spray, with 45-second break between each administration, until 3 puffs (4 IU each) per nostril is reached (total dose 24 IU). Participants were allowed to blow their noses before puffing commenced and will be asked to avoid this until the end of the testing sessions. They will be allowed to dab off any leaking fluid from their noses with a tissue. A stopwatch will be used to time the 45-second breaks, and again after the last puff to keep time until the expected peak levels of oxytocin within the central nervous system (approximately 45 minutes after the administration of the last spray). As this is a randomised crossover trial, participants will receive the oxytocin nasal spray in one session, and the placebo spray in the other. The two sessions are separated by a minimum of 14 days. Following the administration of the sprays and waiting for the sprays to become active within the central nervous system, the researcher will guide participants through a series of experimental tasks, which are described below. Task 1: Oxytocin, heart rate variability, and stress When the participant is comfortable, heart rate will be recorded while participants are prompted to inhale and exhale at regular intervals of 15 cycles per minute for two minutes. Spectral analysis with Fast Fourier Transformation will compute variability in low and high frequency heart periods (HRV). Respiratory sinus arrhythmia (RSA) will be analysed with the peak-to-valley method, calculating the mean difference between the shortest heart R-R period during inspiration and the longest R-R period during expiration. Following the paced breathing task, participants will be asked to complete a cognitive stressor task, the Serial Sevens (SS) task to induce a state of stress. Participants will be instructed to count backwards by sevens (e.g., 1,000, 993, 986, 979 etc.) while the experimenter pressures them to “hurry up” and “go faster” over a period of two minutes. Task 2: Effect of oxytocin on physical functioning Hand strength will be assessed in a standardised way using an isometric hydraulic hand dynamometer “Jamar” (Sammons Preston, Inc, Bolingbrook, IL) in the sitting position with a straight back, shoulder adducted and in a relaxed position, elbow flexed to 90 degrees, and the lower arm and wrist in a neutral position. This test will examine hand strength in the dominant hand of the participant. A single handgrip position will be used and adapted to the hand size of the participants. After maximal squeeze duration of 8 seconds, the peak value will be recorded in kilograms. Recordings will be taken in triplicate, with the mean of the final two trials to be used for statistical and analytic purposes. Lifting ability will be assessed via a modification of the progressive isoinertial lifting evaluation (PILE) protocol, utilised to explore the maximal lifting capacity of the participant. All lifting tests will be executed with a plastic crate and 2.5 kg weight plates which will be added to the crate until the maximum amount of weight is reached. The maximum performance will be recorded in kg. The PILE involves lifting the weights in 1) a lumbar test from floor to waist, and 2) a cervical test evaluating shoulder girdle and upper extremity lift capacity from waist to shoulder height. Participants will begin with a light load (i.e. the weight of the crate and one free weight). Weight is incremented upwards at a rate of the initial free weight following the completion of two repetitions of a lift. A “lifting movement” is defined as a single transfer from one level to the next i.e. from the floor to the waist, or the waist to the shoulder. Both lifts will continue until the participant reaches an end point (see below). The lumbar and cervical PILE tests are done separately, as the norms and biomechanics differ for varying lifting heights. The test will be terminated when the first of the following end-points is achieved: 1) Safety end point: the participant can safely and correctly complete two repetitions of the lift at the highest possible weight load, 25 kg (i.e. the weight of the wooden/plastic crate plus the additional weight plates); or 2) Biomechanical end point: the participant fails to adhere to the correct lifting technique in order to be able to lift the box during the repetitions; or 3) Fear of pain end point: the participant does not want to continue the task because they report they fear they will hurt themselves if they continue the task; or 4) Pain end point: the participant reports that they are in pain At the completion of each paradigm (lifting, handgrip strength), participants will be required to indicate the amount of effort they exerted during the completion of the task on an 11-point numerical rating scale (NRS), with anchors of 0 (no effort at all) and 10 (maximum possible effort). Task 3: Oxytocin and the perception of thermal pain Threshold testing will first be conducted to determine the participant’s individual heat pain threshold on the anterior surface of the dominant arm of the participant. The thermode will be attached to the arm of the participant with the minimum pressure required to ensure that the whole surface of the thermode remains in contact with the skin via a Velcro strap. Three trials will be performed: the first of which will be discarded, and the average threshold from the final two trials will be used in the proposed analyses. All trials will begin with the thermode at a baseline temperature of 32 degrees C, with the thermode increasing in temperature at a rate of 1 degree/second. Each individual trial will end when the participant indicates when they first perceive the thermal stimulation as painful, by pressing a button on the Pathway Response Unit. The thermode then returns to the baseline temperature at a rate of 8 degrees C/second. There will be an interval of 60 seconds between trials. If on any trial the thermode reaches the upper ceiling limit (set at 50 degrees C for safety purposes), the trial will be discontinued and thermal pain tolerance set at 50 degrees C. A total of 9 (3 x 39 degrees C, 3 x 42 degrees C, 3 x 45 degrees C) thermal stimulations will be delivered to each of the target sites (described below) for all participants. The temperatures will be presented in pseudorandomised order. Each trial will begin at a baseline temperature of 32 degrees C and participants will fixate on a crosshair for 2 seconds. The thermode will then increase in temperature so that the target temperature is delivered within 1 second. The target temperature will be maintained for 2 seconds before returning to the baseline temperature over a period of 1 second. Participants will then have 8 seconds to rate the intensity and unpleasantness of the thermal stimulus using a computerised 11-point NRS, with anchors of 0 (no pain/not unpleasant) to 10 (extreme pain/extremely unpleasant). Participants will be asked to select the number on the scale that best represents the intensity and unpleasantness of the pain experience. Site 1: Cervical spine - over the back of the neck, between the hairline and the collar of a t-shirt. Site 2: Deltoid - The point at which the deltoid muscle inserts into the deltoid tuberosity of the humerus Site 3: Tibialis anterior - two thirds of the way up the muscle that runs alongside your shin Task 4: Influence of oxytocin on anxiety and arousal during the anticipation and experience of thermal pain This paradigm employs various anticipatory visual cues that are paired with specific stimulus intensities. There are four stimulus conditions (cue to anticipate either high pain, low pain, no pain or unknown pain) with three stimulus intensities (high pain (45 degrees C), low pain (42 degrees C) and no pain (32 degrees C)). The stimuli will be delivered for 2 seconds to produce intense pain, low pain and innocuous sensations, respectively. These stimuli will be delivered in a pseudorandom and counterbalanced order by the CHEPS thermode, which will be securely attached to the anterior surface of the dominant forearm of the participant. In the experiment, participants will be presented with a black crosshair on a 14 inch laptop screen for 4 seconds before being presented with a cue for 4 seconds, followed by the application of the stimulus over a 4 second period. Heart rate and skin conductance will be recorded throughout the periods of fixation, cue presentation, and stimulus delivery. To verify that both groups of participants have a similar experience with the task and to assess how participants perceived the thermal heat stimuli; all participants will complete ratings after the delivery of each stimulus, using an 11 point NRS ranging from 0 (not at all anxious/no pain/not unpleasant) to 10 (extremely anxious/worst pain/extremely unpleasant) via the following questions: 1) How anxious were you? 2) How intense was it? 3) How unpleasant was it? Instructions Before the commencement of this task participants will receive the following instructions: “In this experiment you will be presented with a series of cues, with painful thermal stimuli following the presentation of each cue. Following each stimulus you will be asked a series of questions relating to how you experienced and perceived the cue and its paired stimulus.” Association between the visual cue and the stimulus delivered As participants are tested twice, different types of cue will be used in each session in an attempt to reduce the carryover/learning effect between the two sessions. Half of the participants recruited will be exposed to the coloured cues in their first session and half of the participants will be exposed to the shape cues in their first session, determined in a pseudorandomised manner. Timing list for experimental tasks: Written informed consent and completion of questionnaires (session 1 only) - 30 minutes Administration of intranasal oxytocin or placebo - 45 minutes Task 1 - 10 minutes Task 2 - 10 minutes Task 3 - 20 minutes Task 4 - 25 minutes Participant debrief - 5 minutes TOTAL Time - 155 minutes