On a day in which patients have an ongoing typical low back pain episode of an intensity of 3 or more (on a numerical rating scale of 0-10), they will undergo all the study measures (see primary outcome measures for detail), except the lumbar MRI: clinical exam, QST, SSRs, CPM, rsMRI, MRS, and blood sample.

On a day in which participants don't have any pain or a pain ranging from 0-2 (on a numerical rating scale of 0-10), an experimental pain state will be induced using a high concentration (8%) Qutenza patch, containing capsaicin. All the study measures will be performed (see primary outcome measures for detail), except the lumbar MRI and blood sample: clinical exam, QST, SSRs, CPM, rsMRI, MRS.

Neurophysiological assessement of sweat activity in response to pain will be recorded with cap electrodes located at the hand. Painful heat stimulation will be applied with a thermode of the Pathway Medoc System. A train of 15 heat stimuli, with an inter-stimulus interval of 13-17 seconds, will be applied. The thermode baseline temperature will be 42ºC and during the stimulation the temperature will quickly ramp up to 52 ºC. Subjects are asked to rate the perception of the stimulus using a pain scale of 0-100. This procedure will be done two times: one at the most painful area of the patients, and the corresponding body area in the matched healthy volunteer, and at the volar forearm as a control pain-free area. This readout is a proxy for sympathetic nervous system activity.

CPM measures the modulation of a noxious test stimulus by another noxious conditioning stimulus applied at a remote body region. In this study, test stimuli of different modalities (pressure, superficial mechanical, heat or electrical stimuli) will be applied at different body regions before and after or before, during and after a cold water bath or neutral water bath (hand immersion) as conditioning stimulus. Changes in test stimuli read-outs (during-before or after-before) will serve as CPM measure. Negative changes represent inhibitory, positive changes facilitatory CPM effects. For all test stimuli read-outs, CPM effects will be expressed as percentage changes. Test stimuli read-outs include: pain ratings on a scale of 0: no pain, to 100: most intense pain; perception thresholds and pain thresholds (in kg for pressure).

Measure of the brain's spontaneous activity acquired during resting state using a 7T Siemens scanner.

Structural resonance image of lumbar spine section acquired using a 3T Siemens scanner.

Imaging method that allows the detection of concentration of certain metabolites in the brain. This data will be acquired using a 3T Phillips scanner.

Blood sample of approximately 14 ml will be drawn, in a total of 3 tubes: PAXGene blood RNA tube, Serum tube, and K2 EDTA tube. This will allow analysis of inflammatory molecules (i.e. cytokines) and cell concentrations (i.e. immune cells).

Pain catastrophizing will be assessed using questionnaires as for example the Pain Catastrophizing Scale (0-52; higher score meaning more catastrophizing).

Pain sensitivity will be assessed using the Pain Sensitivity Questionnaire (PSQ). It consists of 17 items, with an answer range from 0 (not at all painful) to 10 (most severe pain imaginable). The maximum score is 170, where a higher score indicates a higher pain sensitivity.

Pain self efficacy will be assessed using the Pain Self Efficacy Questionnaire (PSEQ). It consists of 10 items, with an answer range from 0 (not at all confident) to 6 (completely confident). The maximum score is 60, where a higher score indicates a higher pain self efficacy / pain coping capacity.

Back awareness will be assessed using the Fremantle Back Awareness Questionnaire. It consists of 9 items, with an answer range from 0 (never) to 4 (always). The maximum score is 36, where a higher score indicates a decreased back awareness.

Central sensitization symptoms will be assessed using the Central Sensitization Inventory (CSI), which consists of two parts.

Part A: includes 25 questions assessing typical central sensitisation symptoms. Each answer is scored on a scale of 0 (never) to 4 (always). A score of more than 40 indicates the presence of central sensitisation.

Part B: determines if the patient has been diagnosed with certain central sensitivity disorder or related disorders, such as anxiety and depression.

Presence of fibromyalgia symptoms will be assessed using the WPI. In the WPI, patients report body areas in which they have had pain in the past week. Each marked area adds one point, to reach a total score of 19.

A patient would meet the criteria for fibromyalgia if:

• WPI score (Part 1) is 7 or higher and SSS score (see below) (Part 2a & b) is 5 or higher OR
• WPI score (Part 1) is from 3 to 6 AND the SSS score (Part 2a & b) is 9 or higher.

Presence of fibromyalgia symptoms will be assessed using the SSS. SSS consists of two parts. In part A patients report the severity of fatigue, waking unrefreshed, and cognitive symptoms. Each question can be answered from 0-3, for a total of 9. The higher the score, the higher the severity of these symptoms. In part B, patients report other somatic symptoms that they have experienced in the past week, reaching a total score of 3. Parts A and B, have a total score of 12 put together.

A patient would meet the criteria for fibromyalgia if:

• WPI score (see above) (Part 1) is 7 or higher and SSS score (Part 2a & b) is 5 or higher OR
• WPI score (Part 1) is from 3 to 6 AND the SSS score (Part 2a & b) is 9 or higher.

Neuropathic pain components will be assessed using PainDETECT, which consists of 9 items: 7 weighted sensory descriptor items (never to very strongly) and 2 items relating to spatial and temporal pain characteristics. A score of 19 or more (out of 38) indicates likely neuropathic pain.

Patients' functional disability will be measured using the Oswestry Disability Index (ODI), which consists of 10 items addressing different aspects of life (i.e. walking, social life, hygiene, etc.). Each item, has a possible 5 point answer. A higher score indicates higher functional disability.

Low back pain patients will be asked to complete pain drawings indicating painful body regions. The painful body area will be calculated as percentage of the whole body area. Higher percentages represent more widespread pain.