Laparoscopic Cholecystectomy for Gallbladder Calculosis in Fibromyalgia Patients: Impact on Musculoskeletal Pain, Somatic Hyperalgesia and Central Sensitization

Abstract

Fibromyalgia, a chronic syndrome of diffuse musculoskeletal pain and somatic hyperalgesia from central sensitization, is very often comorbid with visceral pain conditions. In fibromyalgia patients with gallbladder calculosis, this study assessed the short and long-term impact of laparoscopic cholecystectomy on fibromyalgia pain symptoms. Fibromyalgia pain (VAS scale) and pain thresholds in tender points and control areas (skin, subcutis and muscle) were evaluated 1week before (basis) and 1week, 1,3,6 and 12months after laparoscopic cholecystectomy in fibromyalgia patients with symptomatic calculosis (n = 31) vs calculosis patients without fibromyalgia (n. 26) and at comparable time points in fibromyalgia patients not undergoing cholecystectomy, with symptomatic (n = 27) and asymptomatic (n = 28) calculosis, and no calculosis (n = 30). At basis, fibromyalgia+symptomatic calculosis patients presented a significant linear correlation between the number of previously experienced biliary colics and fibromyalgia pain (direct) and muscle thresholds (inverse)(p<0.0001). After cholecystectomy, fibromyalgia pain significantly increased and all thresholds significantly decreased at 1week and 1month (1-way ANOVA, p<0.01-p<0.001), the decrease in muscle thresholds correlating linearly with the peak postoperative pain at surgery site (p<0.003-p<0.0001). Fibromyalgia pain and thresholds returned to preoperative values at 3months, then pain significantly decreased and thresholds significantly increased at 6 and 12months (p<0.05-p<0.0001). Over the same 12-month period: in non-fibromyalgia patients undergoing cholecystectomy thresholds did not change; in all other fibromyalgia groups not undergoing cholecystectomy fibromyalgia pain and thresholds remained stable, except in fibromyalgia+symptomatic calculosis at 12months when pain significantly increased and muscle thresholds significantly decreased (p<0.05-p<0.0001). The results of the study show that biliary colics from gallbladder calculosis represent an exacerbating factor for fibromyalgia symptoms and that laparoscopic cholecystectomy produces only a transitory worsening of these symptoms, largely compensated by the long-term improvement/desensitization due to gallbladder removal. This study provides new insights into the role of visceral pain comorbidities and the effects of their treatment on fibromyalgia pain/hypersensitivity.

Fig 1. Pain thresholds in control areas in basal conditions (1^st year study).

Means ± SD for all patients’ groups. Significant trend at 1-way ANOVA: P<0.0001 for all parameters (F = 52.251 for EPTs in skin, 45.450 for EPTs in subcutis, 149.21 for EPTs in muscle, 254.60 for PPTs in muscle). The symbols over SD bars denote a significant difference with respect to the other groups.

Fig 2. Patients [FMS+sGb+Cholec] (n = 31).

Linear correlations between number of previously experienced colics and FMS pain, pain thresholds in TePs, electrical and pressure muscle pain thresholds in control areas in basal conditions.

Fig 3. Patients [FMS+sGb] (n = 27).

Linear correlations between number of previously experienced colics and FMS pain, pain thresholds in TePs, electrical and pressure muscle pain thresholds in control areas in basal conditions.

Fig 4. VAS scores of abdominal pain during the first week after laparoscopic cholecystectomy (performed on Day0).

Means ± SD. A: 1^st year study. B: 2^nd year study. Mann-Whitney test for comparison of fibromyalgia groups ([FMS+sGb+Cholec and sGb+Cholec] with the non-fibromyalgia group [sGb+Cholec]). § = significant difference.

Fig 5. FMS symptoms and pain sensitivity in [FMS+sGb+Cholec].

Patients with fibromyalgia (FMS) plus symptomatic gallbladder calculosis (sGb) subjected to cholecystectomy (cholec) during the first year (n. 31, Means ± SD). (A) Spontaneous fibromyalgia pain (VAS); (B) Pain thresholds to pressure stimulation at the 18 Tender Points (TePs); (C),(D),(E) Pain thresholds to electrical stimulation in skin, subcutis and muscle and to (F) pressure stimulation in muscle in control areas (mean of values recorded in trapezius, deltoid and quadriceps). Basis = pre-operative values; 1w, 1m, 3m, 6m, 12m = 1 week, 1 month, 3 months, 6 months and 12 months after cholecystectomy. ANOVA for repeated measures: significant trend, P<0.0001, for all parameters [F = 104.79 for VAS; F = 58.793 for PPTs in TePs; F = 87.673 for skin EPTs, F = 108.48 for subcutis EPTs; F = 132.79 for muscle EPTs; F = 68.439 for muscle PPTs]. In each graph, asterisks over SD bars denote a significant difference with respect to pre-operative values.

Fig 6. Patients [FMS+sGb+Cholec] (n. 31).

Linear correlations between peak postoperative pain and change (decrease) in electrical pain thresholds (EPTs) in muscle of control areas at 1 week and 1 month post-cholecystectomy.

Fig 7. FMS symptoms and pain sensitivity in [FMS+aGb].

Patients with fibromyalgia (FMS) plus asymptomatic gallbladder calculosis (aGb) not subjected to cholecystectomy (n = 28, Means ± SD), followed for a period of 1 year at comparable time points as patients in Fig 5. (A) Spontaneous fibromyalgia pain (VAS); (B) Pain thresholds to pressure stimulation at the 18 Tender Points (TePs); (C),(D),(E) Pain thresholds to electrical stimulation in skin, subcutis and muscle and to (F) pressure stimulation in muscle in control areas (mean of values recorded in trapezius, deltoid and quadriceps). No significant trend for all parameters. ANOVA for repeated measures: for VAS [P = 0.2250; F = 1.409]; for PPTs in TePs [P = 0.8704; F = 0.3670]; for EPTs in skin [P = 0.5311; F = 0.8291]; for EPTs in subcutis [P = 0.2357; F = 1.380]; for EPTs in muscle [P = 0.6849, F = 0.6198], for PPTs in muscle [P = 0.3933, F = 1.046].

Fig 8. FMS symptoms and pain sensitivity in [FMS].

Patients with fibromyalgia (FMS) without gallbladder calculosis (n = 30, Means ± SD), followed for a period of 1 year at comparable time points as patients in Fig 5. (A) Spontaneous fibromyalgia pain (VAS); (B) Pain thresholds to pressure stimulation at the 18 Tender Points (TePs); (C),(D),(E) Pain thresholds to electrical stimulation in skin, subcutis and muscle and to (F) pressure stimulation in muscle in control areas (mean of values recorded in trapezius, deltoid and quadriceps). No significant trend for all parameters. ANOVA for repeated measures: for VAS [P = 0.1200; F = 1.782], for PPTs in TePs [P = 0.8699; F = 0.3679]; for EPTs in skin [P = 0.1460; F = 1.668], for EPTs in subcutis [P = 0.2237; F = 1.411], for EPTs in muscle [P = 0.1109; F = 1.828], for PPTs in muscle [P = 0.1113; F = 1.826].

Fig 9. FMS symptoms and pain sensitivity in [FMS+sGb].

Patients with fibromyalgia (FMS) plus symptomatic gallbladder calculosis (sGb) not subjected to cholecystectomy (n = 27, Means ± SD), followed for a period of 1 year at comparable time points as patients in Fig 5. (A) Spontaneous fibromyalgia pain (VAS); (B) Pain thresholds to pressure stimulation at the 18 Tender Points (TePs); (C),(D),(E) Pain thresholds to electrical stimulation in skin, subcutis and muscle and to (F) pressure stimulation in muscle in control areas (mean of values recorded in trapezius, deltoid and quadriceps). ANOVA for repeated measures: for VAS [P<0.0001; F = 6.203]; for PPTs in TePs [P<0.0006, F = 4.797]; for EPTs in skin [P<0.02, F = 3.155], for EPTs in subcutis [P<0.003; F = 3.916]; for EPTs in muscle [P < 0.0001; F = 12.869], for PPTs in muscle [P < 0.0001; F = 7.530].

Fig 10. FMS symptoms and pain sensitivity in [sGb+Cholec].

Patients with symptomatic gallbladder calculosis (sGb) subjected to cholecystectomy (Cholec) during the 1^st year (n = 26, Means ± SD). Evaluations performed at comparable time points as for patients in Fig 5. (A),(B),(C) Pain thresholds to electrical stimulation in skin, subcutis and muscle and to (D) pressure stimulation in muscle in control areas (mean of values recorded in trapezius, deltoid and quadriceps). No trend for variation in any of the recorded parameters. ANOVA for repeated measures: for EPTs in skin [P = 0.1050; F = 1.866], for EPTs in subcutis [P = 0.2035; F = 1.472]; for EPTs in muscle [P = 0.3216; F = 1.182]; for PPTs in muscle [P = 0.3018; F = 1.224].

Fig 11. FMS symptoms and pain sensitivity in [FMS+sGb with delayed Cholec].

Patients with fibromyalgia (FMS) plus symptomatic gallbladder calculosis (sGb) subjected to cholecystectomy during the second year of study (delayed cholecystectomy) (n = 20, Means ± SD). ANOVA for repeated measures: for VAS, (P<0.0001; F = 33.608); for PPTs in TePs (P<0.0001; F = 89.276, for EPTs in skin (P<0.0001; F = 25.000), for EPTs in subcutis (P<0.0001; F = 52.969), for EPTs in muscle ((p<0.0001; F = 69.778), for PPTs in muscle (p<0.0001; F = 76.896). The asterisk over SD bars indicates a significant difference with respect to basal values.

Fig 12. Patients [FMS+sGb with delayed Cholec] (n = 20).

Linear correlation between peak postoperative pain and change (decrease) in electrical pain thresholds at control sites at 1^st week.

Fig 13. FMS symptoms and pain sensitivity in [FMS+sGb without delayed Cholec].

Patients with fibromyalgia (FMS) plus symptomatic gallbladder calculosis (sGb), not subjected to cholecystectomy (n = 7, Means ± SD) for a period of 2 years. Evaluation performed during the 2^nd year at comparable time points as patients of Fig 11. No significant trend for all parameters. ANOVA for repeated measures: for VAS, (P = 0.1098; F = 1.984), for PPTs in TePs (P = 0.6121; F = 0.7220, for EPTs in skin (P = 0.4864; F = 0.9122), for EPTs in subcutis (P = 0.5140, F = 0.8681), for EPTs in muscle (P = 0.1644; F = 1.703), for PPTs in muscle (P = 0.5311; F = 0.8414).