Risk Factors for Poor Pain Control in Zoster-Associated Pain: A Retrospective Study

ZAP can adversely affect patients’ abilities to perform daily self-care tasks, reduce their QoL, and significantly increase family and socioeconomic burdens [15]. Most cohort or case–control studies have focused on the risk factors and related predictive models of PHN [16, 17], but no study has evaluated factors related to the efficacy of hospitalization in patients with ZAP. To the best of our knowledge, this study was the first to evaluate risk factors affecting the efficacy of drugs plus nerve block therapy. Our study showed that the top risk factors for poor pain control in patients with ZAP treated with drugs plus nerve block therapy were admission NRS and complication with cancer. Sex, BMI, complication with diabetes, ALB, NEU%, and LYM% had little effect on pain control.

Previous studies on risk factors of PHN suggest that advanced age, prodromal pain, severe rash, severe acute pain, eye involvement, diabetes, and severe immunodeficiency are the main factors affecting the pathogenesis of PNH [7, 18, 19]. Our logistic regression analysis showed that higher admission NRS, cancer, and lower RBC count before treatment were independent risk factors for poor pain control in patients with ZAP treated with drugs plus nerve block therapy.

Admission NRS

A meta-analysis by Forbes et al. published in Pain suggests that severe acute pain before treatment is a risk factor for PHN (summary rate ratio [SRR] 2.23; 95% CI 1.71–2.92) [18]. Our study considered admission NRS an independent risk factor for poor efficacy of drugs plus nerve block in ZAP (OR 2.001; 95% CI 1.579–2.537). Higher pain score before treatment often indicated more severe HZ neuritis, more severe peripheral nerve injury, and greater proneness to pain sensitivity changes, including peripheral and central sensitization [19,20,21].

Complication with Cancer

The relationship between HZ and cancer has been drawing more and more attention from clinical and scientific researchers [22, 23]. Qian et al. reported a cohort study indicating that cancer was associated with an increased risk of developing HZ (adjusted hazard ratio [HR] 1.41; 95% CI 1.32–1.52), which was partially compatible with a meta-analysis showing a positive association between HZ and occult cancer [22]. Our study also found a significant correlation between cancer and increasing risk of poor pain control (OR 4.813; 95% CI 1.518–15.259). Patients with cancer have impaired immune function [24], and HZ virus spreads in the skin and even viscera, which is more likely to cause serious complications.

RBC Count

Our results showed that RBC count was closely related to the efficacy of drugs plus nerve block therapy in the treatment of ZAP and that it was significantly lower in patients with poor pain control (P = 0.003). We reviewed the relevant papers on this phenomenon. There are many studies on RBC count and pain [25, 26]. And there have been suggestions that RBC is not only the main undertaker of gas exchange but also the secretor of signal peptide. Hemorphins are endogenous cryptides, belonging to the family of atypical opioid peptides, released during the sequential cleavage of hemoglobin proteins [27]. Hemorphins bind to different opioid receptors affecting pain, perception, and behavior [28]. Neokyotorphin is an atypical analgesic neuropeptide that produces analgesic effect and increases pain threshold by inhibiting the release of γ-aminobutyric acid in the brain [29, 30]. The efficacy of these two molecules has been found to be complementary to that of nerve block therapy. Therefore, we infer that these two blood-derived peptides may be able to explain the correlation between RBC count and pain control. However, further research is needed to determine this relationship. Our study has limitations and there is no further collection and statistics of hemoglobin data. In our prospective cohort study and future research, we will focus on this aspect, hoping to obtain more evidence.

Increase in age has been found to be associated with a sharp increase in PHN risk [18, 31]. However, we found no significant correlation between age and pain control, nor any significant difference in sex distribution between the two groups. In addition, we found significant differences in disease course and ALB levels between the PC and GC groups. The results suggested that patients with chronic HZ pain were more likely to have poor pain control than those with acute HZ pain, which might be related to central sensitization. In addition, ALB levels in the poor control group were low, which might be related to deficits in nutritional status, weak physical condition, and low immunity [32].

Some negative findings in our study were also interesting. Many studies have identified diabetes as a risk factor for PHN [18, 33]. However, our study showed that it was not a risk factor for poor pain control. Our analysis indicated that the nerve block used in clinical work at our center mostly acts on the spinal nerve root or nerve trunk. Diabetes often causes peripheral neuropathy, which would have little effect on pain control in this therapy.

This study addressed the lack of strong research assessing risk factors for poor control of HZ neuropathic pain. However, it has several limitations, such as whether the relevant factors discussed in this article were also risk factors for ineffectiveness of other treatments, whether some risk factors were not considered, and unsatisfactory sample size. In addition, in recent years, our center has adopted nerve radiofrequency modulation therapy or spinal-cord electrostimulation therapy for patients with poor pain control. The spinal-cord electrostimulation therapy has achieved good results, and the research results on the difference between the two treatments need to be further sorted out. In the future, we must continue to study these issues to further confirm our results.

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