The frustrating family of pain

Sabrina Coninx — PhD can­did­ate, Department of Philosophy, Ruhr-Universität Bochum

What is pain? At first glance this ques­tion seems straight­for­ward — almost every­one knows what it feels like to be in pain. We have all felt that shoot­ing sen­sa­tion when hit­ting the funny bone, or the dull throb of a head­ache after a stress­ful day. There is also much com­mon ground with­in the sci­entif­ic com­munity with respect to this ques­tion. Typically, pain is taken to be best defined as a cer­tain kind of men­tal phe­nomen­on exper­i­enced by sub­jects as pain. For instance, this cor­res­ponds to the (still widely accep­ted) defin­i­tion of pain giv­en by the International Association for the Study of Pain (1986). Most cog­nit­ive sci­ent­ists are not merely inter­ested in know­ing that vari­ous phe­nom­en­al exper­i­ences qual­i­fy as pain from a first-person per­spect­ive, how­ever. Instead, pain research­ers primar­ily focus on search­ing for neces­sary and suf­fi­cient con­di­tions for pain, such that a the­ory can be developed which allows for inform­at­ive dis­crim­in­a­tions and ideally far-reaching gen­er­al­iz­a­tions. Pain has proven to be a sur­pris­ingly frus­trat­ing object of research in this regard. In the fol­low­ing, I will out­line one of the main reas­ons for this frus­tra­tion, namely the lack of a suf­fi­cient and neces­sary neur­al cor­rel­ate for pain. Subsequently, I will briefly review three solu­tions to this chal­lenge, arguing that the third is the most prom­ising option.

Neuroscientifically speak­ing, pain is typ­ic­ally under­stood as an integ­rated phe­nomen­on which emerges with the inter­ac­tion of sim­ul­tan­eously act­ive neur­al struc­tures that are widely dis­trib­uted across cor­tic­al and sub­cor­tic­al areas (e.g. Apkarian et al., 2005; Peyron et al., 1999). Interestingly, and per­haps sur­pris­ingly, the activ­a­tion of these neur­al struc­tures is neither suf­fi­cient nor neces­sary for the exper­i­ence of pain (Wartolowska, 2011). Those neur­al struc­tures that are highly cor­rel­ated with the exper­i­ence of pain are not pain-specific (e.g. Apkarian, Bushnell, & Schweinhardt, 2013), and even the activ­a­tion of the entire neur­al net­work is not suf­fi­cient for pain. For instance, itch and pain are pro­cessed in the same ana­tom­ic­ally defined net­work (Mochizuki & Kakigi, 2015). There also does not seem to be any neur­al struc­ture whose activ­a­tion is neces­sary for pain (Tracey, 2011). Even patients with sub­stan­tial lesions in those neur­al struc­tures that are often regarded as most cent­ral for pain pro­cessing are still able to exper­i­ence pain (e.g. Starr et al., 2009).

Figure 1 Human brain processing pain, retrieved from Apkarian et al. (2005). Original picture caption: Cortical and subcortical regions involved in pain perception, their inter-connectivity and ascending pathways. Location of brain regions involved in pain perception are color-coded in a schematic drawing and in an example MRI. (a) Schematic shows the regions, their inter-connectivity and afferent pathways. The schematic is modified from Price (2000) to include additional brain areas and connections. (b) The areas corresponding to those shown in the schematic are shown in an anatomical MRI, on a coronal slice and three sagittal slices as indicated at the coronal slice. The six areas used in meta-analysis are primary and secondary somatosensory cortices (SI, SII, red and orange), anterior cingulate (ACC, green), insula (blue), thalamus (yellow), and prefrontal cortex (PC, purple). Other regions indicated include: primary and supplementary motor cortices (M1 and SMA), posterior parietal cortex (PPC), posterior cingulate (PCC), basal ganglia (BG, pink), hypothalamus (HT), amygdala (AMYG), parabrachial nuclei (PB), and periaqueductal grey (PAG).

Given the dif­fi­culties of char­ac­ter­iz­ing pain by appeal to unique neur­al struc­tures or a spe­cial­ized net­work, some research­ers have attemp­ted to char­ac­ter­ize pain by appeal to neur­osig­na­tures. ‘Neurosignature’ refers to the spatio-temporal activ­ity pat­tern gen­er­ated by a net­work of inter­act­ing neur­al struc­tures (Melzack, 2001). Thus, neur­osig­na­tures are less about the mere involve­ment of an ana­tom­ic­ally defined neur­al net­work, but rather about how involved struc­tures are activ­ated and how their activ­ity is coordin­ated (Reddan & Wager, 2017). Most inter­est­ingly, it has been shown that the neur­osig­na­ture of pain dif­fers from the neur­osig­na­ture of oth­er soma­to­sensory stim­u­la­tions, such as itch and warmth (Forster & Handwerker, 2014; Wager et al., 2013).

Unfortunately, dif­fer­ent kinds of pain sub­stan­tially dif­fer with respect to their under­ly­ing neur­osig­na­tures. For instance, neur­osig­na­tures found in patients with chron­ic pain sub­stan­tially dif­fer from those of healthy sub­jects exper­i­en­cing acute pain (Apkarian, Baliki, & Geha, 2009), because the cent­ral nervous sys­tem of sub­jects who live in per­sist­ing pain is con­tinu­ously reor­gan­ized as the brain’s mor­pho­logy, plas­ti­city and chem­istry change over time (Kuner & Flor, 2016; Schmidt-Wilcke, 2015). At most, there­fore, we can state that a par­tic­u­lar coordin­a­tion of neur­al activ­ity is suf­fi­cient to dis­tin­guish a par­tic­u­lar kind of pain from cer­tain non-pain phe­nom­ena. However, there seems to be no single neur­osig­na­ture that is neces­sary for pain to emerge.

We have arrived at the dilemma that makes pain such a frus­trat­ing object of research. On one hand, research­ers mostly agree that all and only pains are best defined by means of them being sub­ject­ively exper­i­enced as pains. On the oth­er hand, cog­nit­ive sci­ent­ists are unable to identi­fy a single set of neur­al pro­cesses that cap­ture the cir­cum­stances under which all and only pains are exper­i­enced as such. Thus, the sci­entif­ic com­munity has been unable to provide an inform­at­ive and gen­er­al­iz­able account of pain. Two solu­tions to this dilemma have been offered in the literature.

The first solu­tion involves relin­quish­ing the notion of pain as a cer­tain kind of phe­nom­en­al exper­i­ence, which is an ante­cedence for most cog­nit­ive sci­ent­ists. Instead, neur­os­cientif­ic data alone are sup­posed to be the primary cri­terion for the iden­ti­fic­a­tion of pain (e.g. Hardcastle, 2015). This solu­tion there­fore elim­in­ates the first part of the dilemma. There are two main prob­lems faced by this solu­tion. Firstly, neur­al data do not reveal the func­tion of neur­al struc­tures, net­works or sig­na­tures by them­selves. The func­tion of these neur­al char­ac­ter­ist­ics are only revealed by their being cor­rel­ated with some sort of addi­tion­al data (which, in the case of pain, is typ­ic­ally the subject’s qual­i­fic­a­tion of their own exper­i­ence as pain). Thus, remov­ing the sub­ject­ive aspect from pain is ana­log­ous to bit­ing the hand that feeds you. Secondly, ser­i­ous eth­ic­al prob­lems arise when sub­ject­ive exper­i­ence is no longer treated as the decis­ive cri­terion for the iden­ti­fic­a­tion of pain. Because neur­al data may dif­fer from the sub­ject­ive qual­i­fic­a­tion, this approach may lead to a rejec­tion of med­ic­al sup­port for patients that under­go a phe­nom­en­al exper­i­ence of pain. This is a con­sequence that the major­ity of con­tem­por­ary research­ers are — for good reas­ons — unwill­ing to take (Davis et al., 2018).

As a second solu­tion, one might relin­quish the idea that it is pos­sible to devel­op a single the­ory of pain. Instead, research­ers should focus on the devel­op­ment of sep­ar­ate the­or­ies for sep­ar­ate kinds of pain (see, for instance, Jennifer Corns, 2016, 2017). An ana­logy might illus­trate this approach. The gem class ‘jade’ is uni­fied due to the appar­ent prop­er­ties of the respect­ive stones, such as col­or and tex­ture. However, in sci­entif­ic terms the class of jade is com­posed of jadeite and neph­rite, which are of dif­fer­ent chem­ic­al com­pos­i­tions. Thus, it is pos­sible to devel­op a the­ory that enables a dis­tinct char­ac­ter­iz­a­tion with far-reaching gen­er­al­iz­a­tions for either jadeite or neph­rite, but not for jade itself (which lacks a suf­fi­cient and neces­sary chem­ic­al com­pos­i­tion). Similarly, this solu­tion to the pain dilemma holds that all and only pains are uni­fied due to their phe­nom­en­al exper­i­ence as pain, but they can­not be cap­tured in terms of a single sci­entif­ic the­ory. Instead, we need a mul­ti­pli­city of the­or­ies for pain which refer to those sub­classes that reveal a neces­sary and suf­fi­cient neur­al profile.

This solu­tion avoids the meth­od­o­lo­gic­al and eth­ic­al prob­lems faced by the first solu­tion because it is com­pat­ible with pains being defined as a cer­tain sub­ject­ive men­tal phe­nomen­on. However, because this solu­tion denies that it is pos­sible to devel­op a single the­ory of pain, the phe­nomen­on that the sci­entif­ic com­munity is inter­ested in study­ing could not thereby be com­pletely accoun­ted for. If we did devel­op mul­tiple the­or­ies of pain (one for acute pain and one for chron­ic pain, say), it is far from clear that these the­or­ies could explain why all and only pains are sub­ject­ively exper­i­enced as pain. At best, this might explain why cer­tain cases are acute or chron­ic pains, but not why they are both pains. What is miss­ing is a the­or­et­ic­al link that con­nects the dif­fer­ent kinds of pain that, accord­ing to this solu­tion, emerge only as inde­pend­ent neur­al phe­nom­ena in sep­ar­ated the­or­ies. In terms of the pre­vi­ous ana­logy, we need some­thing which plays the role of the resemb­lances in chem­ic­al com­pos­i­tion between jadeite and neph­rite that explains why both of them appear as ‘jade’.

I would like to offer a third solu­tion to the dilemma which avoids the con­cerns faced by the first solu­tion, and which provides the miss­ing the­or­et­ic­al link required by the more prom­ising second solu­tion. This is to hold a fam­ily resemb­lance the­ory of pain. The idea of fam­ily resemb­lance comes from Ludwig Wittgenstein (1953) (although he devel­ops this idea with respect to the mean­ing of con­cepts rather than the prop­er­ties of nat­ur­al phe­nom­ena). A fam­ily resemb­lance the­ory of pain takes the phe­nom­en­al char­ac­ter of pain to uni­fy all and only pains; one’s own sub­ject­ive exper­i­ence of pain as such is the cri­terion of iden­ti­fic­a­tion that picks out mem­bers of the ‘fam­ily’ of pain. Moreover, the fam­ily resemb­lance the­ory of pain denies the pres­ence of an under­ly­ing suf­fi­cient and neces­sary neur­al con­di­tion for pain; there is no neur­al pro­cess that dis­tinct­ively and essen­tially char­ac­ter­izes pain. Thus, the sub­ject­ive qual­i­fic­a­tion iden­ti­fies all and only cases of pain, although they do not share any fur­ther neces­sary or suf­fi­cient neur­al fea­ture. Nonetheless, a fam­ily resemb­lance the­ory fur­ther claims that it is still pos­sible to devel­op a sci­en­tific­ally use­ful neurally-based the­ory of pain that accounts for the phe­nomen­on that the sci­entif­ic com­munity is inter­ested in.

For this third solu­tion, all and only those phe­nom­ena that are exper­i­enced as pain are con­nec­ted through a struc­ture of sys­tem­at­ic resemb­lances that hold between their diver­gent neur­al pro­files. For instance, con­sider, again, acute and chron­ic pain. Both are exper­i­enced as pain, and they are sub­stan­tially dif­fer­ent from each oth­er from a neur­al per­spect­ive when dir­ectly com­pared. However, the trans­form­a­tion from acute to chron­ic pain is a gradu­al pro­cess, whereby the respect­ive dur­a­tion of pain cor­rel­ates with the extent of dif­fer­ences in their neur­al pro­file (Apkarian, Baliki, & Geha, 2009). Thus, the neur­al pro­cess of a pain’s first occur­rence is rel­at­ively sim­il­ar to its second occur­rence, which itself only slightly dif­fers from its third occur­rence, and so forth, until it has trans­formed into some com­pletely dif­fer­ent neur­al phe­nomen­on. This con­nec­tion of resemb­lances over time enables us, how­ever, to explain why sub­jects exper­i­ence all of these kinds of pain as pain: acute and chron­ic pain are bound togeth­er under the fam­ily resemb­lance the­ory through the resemb­lance rela­tions that hold between the vari­ety of pains that con­nect them.

Moreover, the fam­ily resemb­lance the­ory motiv­ates the invest­ig­a­tion of pain’s resemb­lance rela­tions which might prove the­or­et­ic­ally as well as prac­tic­ally use­ful. In fur­ther devel­op­ing research pro­jects of this kind, it appears plaus­ible that, for instance, pains that are more sim­il­ar to each oth­er are more respons­ive to the same kind of treat­ment, even though they do not share a neces­sary and suf­fi­cient neur­al core prop­erty. Understanding the gradu­al trans­ition with­in the resemb­lance rela­tions that lead from acute to chron­ic pain might also offer new pos­sib­il­it­ies of inter­ven­tion. Thus, instead of devel­op­ing a sep­ar­ate the­ory for dif­fer­ent kinds of pain, this third approach motiv­ates the invest­ig­a­tion of the diversity of neur­al pro­files that occur with­in the fam­ily of pain and of the exact struc­ture of their resemb­lance rela­tions, and indeed first steps in this dir­ec­tion are already being taken (e.g. Roy & Wager, 2017).

In sum, when it comes to men­tal phe­nom­ena, such as pain, the under­ly­ing neur­al sub­strate reaches a com­plex­ity and diversity which pre­vents the iden­ti­fic­a­tion of neces­sary and suf­fi­cient neur­al con­di­tions. The fam­ily of pain there­fore con­sti­tutes a frus­trat­ing research object. However, we do not need to throw out the baby with the bathwa­ter and relin­quish the defin­i­tion of pain as a cer­tain kind of men­tal phe­nomen­on, or the idea of a sci­en­tific­ally use­ful the­ory of pain. Of course, a fam­ily resemb­lance the­ory will be lim­ited with respect to its dis­crim­in­at­ive and pre­dict­ive value, since it acknow­ledges that there is no neces­sary or suf­fi­cient neur­al sub­strate for pain. However, it is the most reduct­ive the­ory of pain that can be developed in accord­ance with recent empir­ic­al data, and which can account for the fact that all and only pains are exper­i­enced as pain.

 

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