A systematic literature review concluded that the prevalence of neuropathic pain in the general population was 6.9–10% [27]. In a study investigating the frequency of neuropathic pain among pSS patients, Segal et al. reported that seropositive pSS patients had %36, seronegative pSS patients had %40 neuropathic pain [10]. In addition, Yolcu et al. reported the presence of neuropathic pain in 36% of 36 pSS patients [28]. In our study, we found that neuropathic pain in our cohort was 29.2%, which is almost similar to prior studies in the literature.

Neuropathic pain associated with peripheral nerve involvement can be occurred by means of various mechanisms [29, 30]. Abnormal or hyperactivity of SFN nociceptive thin myelinated (A delta) and unmyelinated (C) fibers may cause neuropathic pain [31]. Additionally, it has been thought that nociplastic pain might be a component of neuropathic pain or a distinct entity [32]. Neuropathic pain is occurred with central sensitization results from reorganization (plasticity), sensitization (hyperexcitability), or reduced inhibition of nociceptive neurons in the central nervous system by NMDA receptor activation [29]. Fibromyalgia pain may also be secondary to central sensitization (nociplastic pain) [33].

Neuropathic pain can typically present as continuous pain (burning, squeezing, pressure), paroxysmal pain (sensations resembling electric shocks or stabbing pain), triggered pain (allodynia), or paresthetic and dysesthetic sensations (tingling, prickling). Due to the heterogeneity of neuropathic pain, the underlying mechanisms remain unclear. Continuous pain has been associated with both peripheral and central mechanisms, and may be related to the activation of C nociceptor axons in the skin or central hyperactivity resulting from deafferentation [34, 35]. On the other hand, paroxysmal pain originates from peripheral hyperexcitable nociceptive fibers [36]. Allodynia can also arise as a result of central sensitization [37].

Neuropathic complaints are prominent in the presence of SFN in pSS and non-pSS patients [38,39,40]. However, neuropathic symptoms (such as pricking, tingling, numbness, itching, burning sensations, and electric shocks) could not be differentiated in 30 patients with pSS, regardless of the presence or absence of SFN [40]. A deeper understanding of neuropathic and nociplastic pain might be important in terms of additional symptoms such as urological complaints accompanying in pSS.

LUTS is a description rather than a diagnosis. Voiding and storage symptoms are evaluated by means of some questionnaire forms [41]. For example, LUTS are evaluated with the IPSS form. Three questions in the IPSS form assess storage (frequency, urgency, and nocturia) and four questions assess voiding symptoms (intermittency, incomplete voiding, weak urine flow, and hesitant urination). The OAB-V8 questionnaire form can be used to inquire about OAB symptoms. In addition, urination frequency, amount and quality of life are inquired with the ICIQ-SF questionnaire form. While storage complaints may indicate conditions such as OAB and/or detrusor overactivity, voiding complaints may suggest detrusor underactivity and/or bladder outlet obstruction [16].

A cohort study has found an increased risk of OAB and bladder pain syndrome/interstitial cystitis in patients with pSS [42]. In the etiology of bladder pain syndrome/interstitial cystitis, dysfunction of the bladder urothelium, neurogenic inflammation, and neuropathic pain are discussed. Neurogenic inflammation occurs due to the release of inflammatory mediators by afferent neurons, creating a cycle in which activated inflammatory cells stimulate neurons, leading to increased sensitivity and subsequent release of more inflammatory mediators.

In reviewing the literature, it can be seen that studies conducted to determine the prevalence of LUTS in pSS patients are reported in a wide range. Haarala et al. analysed the data from 36 pSS patients and reported that the frequency of severe LUTS 14% among in pSS patients [43]. In a study including 21 secondary SS patients, severe LUTS was reported in 19% [44]. Another study conducted with 71 pSS patients, showed that the rate of severe LUTS was 61% [6]. The current study found that the prevalence of moderate and severe LUTS in pSS patients was 43.1%. The difference of prevalence rates may be explained due to the various in the number of patients in the studies.

In this study, patients with pSS were divided into two sub-groups according to the presence/absence of neuropathic pain. IPSS and IPSS voiding subscores of neuropathic pain group were significantly higher than non-neuropathic pain group. IPSS storage, OAB-V8 and ICIQ-SF scores were higher in the neuropathic pain group, although there was no statistically significant difference. These results suggest that the presence of neuropathic pain in pSS may be related to detrusor underactivity and/or bladder outlet obstruction.

In our study, 43 patients (59.7%) were postmenopausal. The median IPSS score for premenopausal patients was 5 (IQR 11), compared to 7 (IQR 10) for postmenopausal patients. However, there were no statistically significant differences between these two groups in terms of IPSS or its subgroups. Additionally, out of 56 patients questioned about vaginal dryness, 26 (46.4%) reported experiencing it. The median IPSS score for patients without vaginal dryness was 4.5 (IQR 9), while those with vaginal dryness had a median IPSS score of 6.5 (IQR 12). Again, no statistically significant differences were observed in IPSS or its subgroups between these two groups. While hormonal changes, particularly postmenopausal atrophic changes, are discussed in the literature as potential contributors to LUTS [45], our findings did not support a significant impact in this cohort. This suggests that factors other than hormonal alterations might play a more prominent role in the development of LUTS in pSS patients. Further studies with larger populations may be needed to explore this relationship more thoroughly.

In a study conducted with type 2 diabetic patients, it has revealed that detrusor underactivity was associated with A-delta and C-fiber bladder afferent pathways, which are among the neuropathic pain pathways [46]. The prevalence of SFN is approximately 52.95 per 100,000 population, with diabetes and idiopathic origins being the most common etiologies. Symptoms often present in a length-dependent pattern and include dysesthesia, allodynia, pain, burning sensations, and coldness. Additional autonomic features, affecting urinary, gastrointestinal or cardiovascular systems, are common but often poorly documented [47]. SFN is diagnosed based on intraepidermal nerve fiber density, quantitative sensory and autonomic tests, alongside normal nerve conduction studies [47]. In another study with 51 patients among chronic pelvic pain suggested that detrusor underactivity and/or bladder outlet obstruction may be associated with SFN [48]. In a study involving 39 patients, where skin punch biopsies were performed to detect SFN positivity, SFN positivity was found in 64% of the patients [49]. Patients reported a combination of pain characteristics, including pain when the bladder is full, urethral pain during and after urination, pain on the vulvar or scrotal surface, and deep pain in the vagina, penis, or rectum during sexual activity or at rest [49]. On the other hand, Tarhan et al. found the OAB-V8 score to be 56% positive (> 8 points) in 50 pSS patients and stated that the frequency of OAB was high in pSS [4]. In this study, OAB-V8 positivity was found 54.2% among 72 pSS patients.

The current study has several limitations. First, there is no healthy control group included. Second, it is possible that the amount and type of fluid ingested by pSS patients could be contribute for their LUTS. However, we were unable to record the amount of fluid intake or caffeine consumption by the patients. Finally, the evaluation of patients with LUTS and neuropathic pain symptoms was limited to symptom score questionnaires, and no invasive procedures were performed.