Neuropathic pain (NeP) probably concerns 7-8% of the general population 12. In addition to a number of patients with various neurological diseases 3, NeP affects significant proportions of patients with diabetes 4, low back pain 5, post-surgical pain 6, cancer 78 and some infectious diseases 9 and has a major impact on quality of life.

Neuropathic pain syndromes are rather heterogeneous and the relationship between a certain etiology and the symptoms reported by patients are not straightforward. Different symptoms (i.e., allodynia, burning or paroxysmal pain) may coexist in the same patient and may reflect different mechanisms of disease 10. Consistent with this hypothesis, it has been shown that different symptoms or symptom combinations may respond differently to treatment 111213. These data highlight the importance of a specific measurement of neuropathic pain symptoms or neuropathic components, to assess the effects of treatment both in clinical trials and in daily practice.

Only two questionnaires have been specifically developed to assess the effects of treatment in neuropathic pain syndromes 1415. To date, the only tool that has been validated in neuropathic pain syndromes of both central and peripheral origins is the Neuropathic Pain Symptom Inventory (NPSI). Also, it is the sole that has underwent factorial analysis confirming that the qualities of the symptoms measured by this inventory reflect distinct clusters of symptoms (i.e. dimensions) with a putative common mechanistic background 1015.

Here we validated the translated Portuguese version of the NPSI (PV-NPSI) 16. Portuguese is spoken by 240 million people and in the main language in more than ten countries in America, Europe, Africa and Asia 17. So far, the NPSI has been translated into more than 60 languages, but its multidimensional structure has only been confirmed into Italian 18 and Spanish 19.

After translation of the NPSI from the original French version and verification of its cultural and conceptual adequacy in Brazilian patients 16, the psychometric validation of the Brazilian Portuguese version of the NPSI was performed in one hundred consecutive patients with neuropathic pain seen in our outpatient pain clinic from January to July 2009. The study was approved by our I nstitution's Ethics Review Board (Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil), and written informed consent was obtained from all participants.

Neuropathic pain is common 27, and its prevalence in certain populations of patients is particularly high, such as in diabetics, cancer, and HIV patients 828. Different screening tools have been proposed to identify patients with a higher probability to present neuropathic pain, such as the LANSS 2930 and the DN-4 2. These tools have been translated and validated in different languages and are used broadly in clinical trials and epidemiological studies 731. Only two scales were specifically created and validated to assess neuropathic pain syndromes 1415. The NPSI is the only tool validated in patients with neuropathic pain of central and peripheral origin and has a factorial design validated in a broad range neuropathic pain patients.

The present study described the psychometric validation of the Portuguese version of the NPSI. The validation process showed that the present version of the self-questionnaire is: (i) valid and reliable; (ii) it is sensitive to changes in neuropathic pain of both central and peripheral origin; and (iii) it assessed different aspects of neuropathic pain.

The PV-NPSI was filled out in a relatively short period of time making it suitable for the use in clinical practice and in clinical studies. All descriptors were reported in a significant frequency of patients, with a prevalence of 65%. We assessed the test-retest validity of the inventory in those patients who did not present any change in their pain intensity between both visits. The PV-NPSI was reliable in this setting, with a good intraclass correlation for all items.

The total score of the PV-NPSI in the 1^st and 2^nd visits correlated with the visual numeric scale score in each of these sessions. However, the change in the PV-NPSI from the 2^nd to the 1^st visit only weakly correlated to the changes in the VNS score between both instances. This is similar to what was found in the original version of the NPSI 15. Interestingly, GIC scores in the second visit showed a high correlation with the change in the PV-NPSI between both visits, while the change in the VNS score only moderately correlated with the GIC scores. This attests that in this population of neuropathic pain patients, the total score of the PV-NPSI was better suited to assess neuropathic pain characteristics than the VNS score, showing good validity and reliability.

The factorial analysis showed that the PV-NPSI assessed different components of neuropathic pain. Five different factors were found. The first factor included evoked pain (i.e. pain evoked by brushing, pressure or contact with cold) and two spontaneous pain descriptors (squeezing and pressure). Two paroxysmal descriptors (stabbing and pins and needles) were clustered in a second factor. The three remaining descriptors were grouped in one factor each (burning pain, electric shocks and tingling). Some of the cluster patterns were slightly different from the original version where spontaneous pain and paroxysmal descriptors were clustered in a single factor each. These differences probably reflect different valences of each descriptor between the two populations 15.

Neuropathic pain is a rather heterogeneous entity and different symptoms may be caused by a single etiological factor, thus suggesting it is a "trans-etiological" entity 10. Neuropathic pain symptoms are thought to reflect specific pain mechanisms. Two main approaches have employed questionnaires based on pain characteristics to broaden our knowledge on this topic. One used these tools to gain mechanistic insights on this pain syndrome. For example, it has been shown that the intensity of ongoing pain, as detected by the NPSI inversely correlated to the amplitude of laser evoked potentials in patients with painful distal polyneuropathy, suggesting that damage to intra-epidermal nociceptive terminals would be implicated in this specific symptom of NeP 32. In another study, it has been shown that patients presenting exclusively with spontaneous pain according to the NPSI significantly differed from those also presenting with evoked pain. Isolated spontaneous pain was highly correlated with a greater decrease in white matter tract metrics seen under tractography, suggesting a more intense injury to the somatosensory system. Also, the presence of evoked pain in the NPSI was associated with a more discrete spinothalamic dysfunction as assessed by laser-evoked potentials when compared to patients without this pain symptom 33. This supports the idea that different aspects of neuropathic pain as assessed by the NPSI are associated with different anatomical dysfunctions and pathophysiological backgrounds in patients with NeP. Another use of these tools was to to guide mechanism-based approaches to NeP treatment, since it has been increasingly shown that the efficacy of pharmacological treatment may vary depending on the presence of certain symptoms (mechanisms) of neuropathic pain 123435.

In conclusion, the psychometric properties of the PV-NPSI render it adequate to evaluate patients with both central and peripheral neuropathic pain syndromes. The reliability of the different descriptors was adequate and sensitive to change and the NPSI may help select subgroups of NeP patients with different anatomical and mechanistic dysfunctions, and possibly different response to treatment.

The authors declare that they have no competing interests.

Study Design: DCA, DB, MJT. Data Collection: CMN, AFB, LTY, JA, PRNS, HelenaHK, KS. Data bank feeding: TZ, RG. Statistical analyses: DCA, ETF. Manuscript writing: DCA, KASLF. Manuscript revising: DB, MJT. All authors read and approved the final manuscript.