The effect of nonrecurring alcohol administration on pain perception in humans: a systematic review

Figures & data

Table 1 Search query

(alcohol OR ethanol) and (analgesia OR analgesic effect OR analgetic effect OR pain perception) NOT animals NOT block NOT cancer NOT chronic NOT injection NOT management NOT mice NOT rats NOT surgery NOT review NOT topical NOT withdrawal

Table 2 Experimental measures of pain perception

Measure of pain perception	Description
Pain threshold	Stimulus intensity that is experienced as beginning pain
Pain tolerance	Maximum stimulus intensity that can be tolerated
Pain intensity	Subjective evaluation of the degree of pain sensation evoked by a certain stimulus on a rating scale (NRS or VAS)
Pain unpleasantness	Subjective evaluation of the degree of pain-related negative effect evoked by a certain stimulus on a rating scale (NRS or VAS)

Abbreviations: NRS, numerical rating scale; VAS, visual analog scale.

Table 3 General design of studies

Reference	Subjects			Experimental manipulations
	N	Age, years (mean [M]/range)	Sex	Design	Placebo control	Blinding	Randomization	Baseline control
19a	60	M=23.60	Mixed	Within subject	Yes	Double blind	Yes	Yes
20a	48	M=23.71	Mixed	Within subject	Yes	Double blind	Yes	Yes
22	8	19–28	Mixed	Within subject	Yes	Double blind	Yes	Yes
21	11	M=24	Mixed	Within subject	Yes	Double blind	Not specified	No
27	81	18–30	Male	Between subject	Yes	Double blind	Not specified	Yes
23	18	21–30	Female	Within subject	Yes	Double blind	Yes	Yes
26	8	M=31.90	Male	Within subject	No	Not specified	Yes	No
30	20	M=37.45	Male	Within subject	Yes	None	Yes	Yes
29	52	M=35.0	Male	Between subject	Yes	None	Yes	Yes
32	8	Not reported	Male	Within subject	Yes	Double blind	Yes	Yes
25	50	M=38.6	Male	No control condition	No	None	No	Yes
28, experiment 1b	7	Not reported	Male	Within subject	Yes	Single blind	Yes	Yes
28, experiment 2b	7	Not reported	Male	Within subject	No	Single blind	Yes	Yes
1	51	Not reported	Male	Between subject	Yes	Double blind	Yes	Yes
24	79	M=44.3	Male	No control condition	No	None	No	Yes

Notes:

a As these two publications derive from the same experimental investigation, they are counted as one experiment;

b as this investigation contains the results of two experiments, both experiments are listed separately.

Table 4 Characteristics of alcohol administration

Reference	Mode of administration	Time interval for consumption of drink	Administered dose of alcohol (g/kg)a	Interval between alcohol administration and pain testing	Assessment of BAC/BrAC	Mean BAC/BrAC (mg/dL)
19c,20c	IV	Not applicable	Low dose: 0.38; high dose: 0.94b	30 minutes after targeted BAC had been reached	Continuous monitoring (clamp procedure)	Low dose: 43.7; high dose: 100
22	Oral	10 minutes	0.7 for females; 0.8 for males	120 minutes after start of the drink	Assessment of BAC 0, 20, 65, 75, and 120 minutes after start of the drink	84 (65 minutes postdrink)
21	Oral	10 minutes	Low dose: 0.25; high dose: 0.5	55–60 minutes after start of the drink	Assessment of BrAC 15, 55, 80, 110, and 140 minutes after completion of drink	Low dose: 31/20; high dose: 62/54 (15/55 minutes postdrink)
27	Oral	15–20 minutes	Active placebo: 0.10; low dose: 0.38; medium dose: 0.57; high dose: 0.76	10–15 minutes after completion of the drink	Assessment of BrAC immediately after pain testing	Active placebo: 1; low dose: 63; medium dose: 85; high dose: 88
23	Oral (placebo IV)	Not reported	0.8	90 minutes after completion of the drink	Not assessed/reported
26	Oral	15 minutes	0.8	45 minutes after start of the drink	Assessment of BAC 45 minutes and 60 minutes after start of the drink	Before pain testing: 76; after pain testing: 71
30	Oral	20 minutes	0.5	35 minutes after start of the drink	Assessment of BrAC 37 minutes after start of the drink	60
29	Oral	10 minutes	0.244	25 minutes after start of the drink	Not assessed
32	IV		Loading dose of 0.6 followed by a constant infusion of 0.002	35 minutes after start of alcohol infusion	Assessment of BrAC immediately after pain testing	87
25	Oral	Drink 1: 15 minutes; drink 2: 20 minutes	Drink 1: 0.261; drink 2: 0.521 (total: 0.782)	15 minutes after ingestion of each drink	Not assessed	Not assessed
28, experiment 1d	IV	Not applicable	1.2	15, 30, 45, and 60 minutes after start of infusion	Assessment of BAC every 15 minutes	Data not reported
28, experiment 2d	IV	Not applicable	0.6	15, 30, 45, and 60 minutes after start of infusion	Assessment of BAC every 15 minutes	Data not reported
1	Oral	Not reported	Low dose: 0.32; high dose: 0.63	40 minutes after start of the drink	Assessment of BrAC immediately before and after pain testing	Data not reported
24	Oral	Not reported	Drink 1: 0.261; drink 2: 0.521 (total: 0.782)	Not specified	Not assessed	Not assessed

Notes:

a Indication of quantity of the administered dose has been transformed in g/kg of 100% alcohol for a better comparability between studies;

b amount of alcohol adjusted to reach a targeted BAC by using a clamp procedure;

c as these two publications derive from the same experimental investigation, they are counted as one experiment;

d as this investigation contains the results of two experiments, both experiments are listed separately.

Abbreviations: BAC, blood alcohol concentration; BrAC, breath alcohol concentration; IV, intravenous.

Table 5 Methods of pain induction and pain measurement and main results concerning alcohol effects on pain perception

Reference	Sample	Design	Pain induction	Measure of pain perception	Main findings regarding alcohol effect on pain measures	Additional findings regarding moderating variables
20	Subsample of Perrino et al,^Citation19 N=48 (25 male; (31 FHN, 17 FHP; 28 low Ne, 20 high Ne)	Within subject: high alcohol, low alcohol, placebo Between subject: family history of alcoholism (positive vs negative), Ne (high vs low)	Electrical stimulation (volar surface of the distal forearm)	Pain threshold Pain tolerance (half-maximal pain intensity)	Pain threshold: no alcohol effect Pain tolerance: pain-dampening effect of alcohol	Family history of alcoholism and neuroticism: Interaction effect: increased pain tolerance after low dose in subjects with high Ne and FHP No influences of these variables on alcohol effects after the high dose
19	N=60 (32 male; 41 FHN, 19 FHP)	Within subject: high alcohol, low alcohol, placebo Between subject: family history of alcoholism (positive vs negative)	Electrical stimulation (volar surface of the distal forearm)	Pain threshold Pain tolerance (half-maximal pain intensity)	Pain threshold: no alcohol effect Pain tolerance: pain-dampening effect of alcohol	Family history of alcoholism: Pain-dampening effect only in FHN subjects Sex: No influence on pain perception or effect of alcohol on perception Mood: Pain-dampening effect of alcohol unrelated to alterations in mood
22	N=8 (4 male)	Within subject: alcohol vs placebo	von Frey hairs	Pain threshold Pain intensity rating (VAS 0–10)	Pain threshold: no alcohol effect Pain rating: no alcohol effect	No moderating variables assessed
21	N=11 (9 male)	Within subject: high-dose alcohol vs low-dose alcohol vs placebo	Cold pressor test (3 minutes, nondominant arm)	Pain intensity rating (VAS 0–10) Pain discomfort rating (VAS 0–10) McGill Pain Questionnaire (short form)	Pain intensity rating: no alcohol effect Pain discomfort rating: no alcohol effect McGill Pain Questionnaire: no alcohol effect	No moderating variables assessed
27	N=81 (all male; 39 FHP; 42 FHN)	Between subject: active placebo vs low-/medium-/high-dose alcohol; family history of alcoholism (positive vs negative)	Electrical stimulation (inside of the right elbow)	Pain intensity rating (NRS 0–10) Pain discomfort rating (NRS 0–10)	Pain intensity rating: pain-dampening effect of the high alcohol dose; increase in perceived pain in the active placebo group Pain discomfort rating: pain-dampening effect of the medium and high alcohol doses	Family history of alcoholism: FHP men reported more pain and discomfort overall during shock Alcohol reduced differences to the FHN group Drinking behavior: Pain-dampening effect of alcohol unrelated to self-reported drinks per week
23	N=14 (all female)	Within subject: saline (IV) vs morphine (IV) vs sulfate (IV) vs alcohol (orally)	Pressure (Achilles tendon)	Pain threshold Pain tolerance	Pain threshold: no alcohol effect Pain tolerance: pain-dampening effect of alcohol comparable with that of morphine	No moderating variables assessed
26	N=8 (all male)	Within subject: sober vs alcohol	Electrical stimulation	Scale calibration (“definitely unpleasant”) Pain intensity rating (VAS 0–10) Pain discomfort rating (VAS 0–10)	Scale calibration: pain-dampening effect of alcohol Pain intensity rating: pain-dampening effect of alcohol (same rating compared with sober condition despite higher intensity) Pain discomfort rating: pain-dampening effect of alcohol (lower rating compared with sober condition despite higher intensity)	No moderating variables assessed
30	N=20 (all male)	Within subject: alcohol vs placebo vs control Between subject: naloxone vs saline; drinking experience	Cold pressor test (1 minute; hand to the wrist)	Slope index of increasing pain (on the basis of verbal report at intervals of 5 seconds)	Slope index of increasing pain: pain-dampening effect of alcohol Naloxone condition: no main effect of naloxone administration	Drinking experience (DAS)^Citation47: No interaction effect of drinking experience with alcohol analgesia Interaction with naloxone condition: naloxone enhanced analgesia among men with low DAS scores and reversed analgesia among men with high DAS scores
29	N=56 (all male)	Between subject: alcohol vs placebo; alcohol vs placebo instruction; drinking experience	Cold pressor test (1 minute; hand to the wrist)	Highest level of verbal report at intervals of 5 seconds	No main effects of alcohol reported	Drinking experience: Interaction of drinking experience and beverage instruction on pain reports. Men with high scores on two scales showed reduced pain when told they had consumed alcohol and increased pain when told they had consumed tonic
32	N=8 (all male)	Within subject: alcohol vs morphine; before vs after naloxone injection	Pressure (bare area of the tibia)	Pain threshold	Pain threshold: pain-dampening effect of alcohol and morphine; no differences between the treatments No effect of naloxone on pain in the alcohol condition; decrease of threshold in the morphine condition	No moderating variables assessed
25	N=50 (all male)	Between subject: customary drinking	Cold pressor test (40 seconds; arm to the elbow)	Highest level of verbal report at intervals of 5 seconds	No main effects of alcohol reported	Customary drinking (Williams Problem Drinking Inventory): Pain reduction after alcohol consumption was correlated with three items (drinking to forget problems, drinking to be satisfied with oneself, drinking to increase self-confidence)
28, experiment 1a	N=7 (all male)	Within subject: alcohol vs placebo	Pressure (bare area of the tibia)	Pain threshold	Pain threshold: pain-dampening effect of alcohol	No moderating variables assessed
28, experiment 2a	N=7 (all male)	Within subject: alcohol vs morphine	Pressure (bare area of the tibia)	Pain threshold	Pain threshold: pain-dampening effect of alcohol and morphine; no significant difference between the treatments	No moderating variables assessed
1	N=51 (all male)	Between subject: high alcohol vs low alcohol vs placebo; customary drinking	1. Pressure (2 minutes, middle phalanx of the index finger) 2. Cold pressor test (2 minutes, hand to the wrist)	Pain threshold Pain intensity rating (NRS 0–10)	No main effects of alcohol reported	Customary drinking: Customary bar drinkers experienced greater pain reduction with the high alcohol dose than customary family drinkers Pressure pain: heightened pain threshold and lower pain report in 1 minute for subjects with a history of frequent sickness after drinking after the high alcohol dose Cold pain: greatest pain reduction when subjects were given their customary dose Pain increased in the control condition in average and heavy drinkers
24	N=79 (all male)	Between subject: alcoholism	Cold pressor test (40 seconds, arm to the elbow)	Highest level of verbal report at intervals of 5 seconds	Alcohol effect dependent on group	Alcoholism: Pain-dampening effect of alcohol only in alcoholics; nonalcoholics showed no changes in pain levels

Notes:

a as this investigation contains the results of two experiments, both experiments are listed separately.

Abbreviations: FHN, family history negative; FHP, family history positive; Ne, neuroticism; VAS, visual analog scale; NRS, numerical rating scale; IV, intravenous; DAS, Definitions of Alcohol Scale.

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