The Role of Descending Modulation in Manual Therapy and Its Analgesic Implications: A Narrative Review

Table 1

Neurophysiological response to manual therapy variations.

Study	Subjects	Control/sham	Variation	Findings
Degenhardt et al. [38]	7 women and 3 men with () and without () low back pain	Light touch	OMT	↑ β-endorphins; ↑ PEA
McPartland et al. [39]	Osteopathic patient population ()	Sham manipulation	OMT	↑ AEA
Vernon et al. [40]	27 healthy males	() Control group laid supine on a treatment table; () Sham group received joint play maneuvers	SMT	↑ β-endorphins
Christian et al. [42]	40 male subjects who were chiropractic patients and students with and without pain	Sham (joint taken to end-range of motion)	SMT	→ β-endorphins
Sanders et al. [43]	9 males and 9 females with acute (<2 weeks) low back pain	Sham group () received light touch at L4/L5–S1	SMT	→ β-endorphins
Plaza-Manzano et al.; [44]	30 graduate school students	No treatment	SMT	↑ orexin A; ↓ neurotensin; ↓ oxytocin
Skyba et al. [47]	113 male Sprague-Dawley rats	() Vehicle w/manipulation; () Vehicle w/anesthesia; () Drugs w/anesthesia	Knee manipulation	Serotonin-mediated; Norepinephrine-mediated; Non-GABA-mediated
Martins et al. [48]	8 male Swiss mice per group	() Control; () Sham	Ankle joint mobilization	EO-mediated^†
Martins et al. [49]	8 male Swiss mice per group	() Control; () Sham	Ankle joint mobilization	CBR-mediated^†
Martins et al. [50]	8 male Swiss mice per group	() Control; () Sham	Ankle joint mobilization	Adenosine-mediated^†
Martins et al. [53]	8 adult male Wistar rats per group	() Sham; () Sham w/anesthesia; () Sham w/mobilization; () Crush; () Crush w/anesthesia	Ankle joint mobilization	↓ glial cell activation
Paungmali et al. [56]	7 females and 17 males with lateral epicondylalgia	() Placebo; () Control	MWM	No increase in tolerance over treatment period
Paungmali et al. [55]	4 females and 14 males with lateral epicondylalgia	() Placebo; () Control	MWM	Non-EO-mediated^†
Santos et al. [61]	Male Wistar rats	() Control; () Injury only; () Sham; () Sham w/mobilization	NM	Dynorphin-mediated
Kaada  and  Torsteinbø; [64]	6 male and 6 female subjects with a history of myalgia		Connective tissue massage	↑ β-endorphins
Trentini et al. [66]	Male and female Sprague-Dawley rats	() Control; () Placebo	Acupressure	EO-mediated^†
Fassoulaki et al. [67]	4 females and 8 males without a familiarity with acupuncture	() Control; () Sham	Acupressure	→ β-endorphins
Day et al. [68]	17 women and 14 men who were healthy and free of pain	Control	Conventional massage	→ β-endorphins; → β-lipotropins
Agren et al. [69]	13–21 male Sprague-Dawley rats	Control	Conventional massage	Oxytocin-mediated^†
Turner et al. [70]	26 nulliparous women that cycle	() Positive emotion; () Negative emotion	Conventional massage	↑ oxytocin
Bello et al. [71]	14 males	Control	Conventional massage	↑ oxytocin; → arginine vasopressin
Morhenn et al. [72]	50 females and 45 males	Rest	Conventional massage	↑ oxytocin; ↓ β-endorphins
Hernandez-Reif et al.; [73]	13 women and 11 men with >6 months low back pain	Relaxation therapy	Conventional massage	↑ dopamine; ↑ serotonin
Hernandez-Reif et al.; [74]	34 women with stage 1 or 2 breast cancer	Control (medical treatment only)	Conventional massage	↑ dopamine; ↑ serotonin
Field et al. [75]	Review		Conventional massage	↑ dopamine; ↑ serotonin
Hart et al. [76]	Nineteen women with anorexia nervosa	Control (standard treatment only)	Conventional massage	↑ dopamine
Lund et al. [77]	19 fibromyalgia patients	Guided relaxation	Conventional massage	↑ corticotropin releasing factor
Billhult et al. [78]	32 women with breast cancer	Attention	Conventional massage	↑ oxytocin
Tsuji et al. [79]	7 Japanese boys with Autism Spectrum Disorder and their mothers	Control (no massage, crossover)	Conventional massage	↑ oxytocin
Rapaport et al. [80]	29 females and 24 males	Light touch	Conventional massage	→ oxytocin; ↓ arginine vasopressin
Rapaport et al. [81]	23 females and 22 males	Light touch	Conventional massage	↑ oxytocin (acute); → oxytocin (chronic)

denotes review; † denotes a conclusion inferred from naloxone or relevant antagonistic response.